Automated staining system and reaction chamber

ABSTRACT

An apparatus including a reagent cartridge and a reaction chamber, the reagent cartridge having a reagent capsule removably positioned therein for dispensing of a reagent onto the reaction chamber. A system including a linearly translatable mounting assembly having a plurality of mounting stations dimensioned to receive at least one fluid dispensing cartridge, a linearly translatable bulk reagent dispensing assembly having a plurality of bulk reagent dispensing nozzles coupled thereto and a receiving assembly positioned beneath the mounting assembly and the bulk reagent dispensing assembly, the receiving assembly including a plurality of reaction stations. A method including determining an inventory of an automated sample processing system, downloading a processing protocol from a central controller to the automated sample processing system, operating the automated sample processing system based on the processing protocol and independently of the central controller and dispensing a reagent from the automated sample processing system.

BACKGROUND

1. Field

An automated staining system, in particular an automated staining systemfor processing biological specimens.

2. Background

In various settings, processing and testing of biological specimens isrequired for diagnostic purposes. Generally speaking, pathologists andother diagnosticians collect and study samples from patients, andutilize microscopic examination, and other devices to assess the samplesat cellular levels. Numerous steps typically are involved in pathologyand other diagnostic processes, including the collection of biologicalsamples such as blood and tissue, processing the samples, preparation ofmicroscope slides, staining, examination, re-testing or re-staining,collecting additional samples, re-examination of the samples, andultimately the offering of diagnostic findings.

Tissue processors can be operated with varying levels of automation toprocess human or animal tissue specimens for histology or pathologyuses. Various types of chemical reagents can be used at various stagesof tissue processing and various systems have been developed fordelivering reagents to specimen containing slides. Examples of knownreagent delivery systems include small quantity release dispensers,manual pouring into reagent vats, or via bulk containers connected witha processor via tubing.

There are various disadvantages of known systems. For example, manuallypouring into, or draining, reagent vats is time consuming and requirespouring accuracy, thereby decreasing the overall efficiency of thetissue processing system. Another disadvantage is that manually pouringand draining reagents can be sloppy, requiring clean-up of spills andconsequential instrument down-time. A further disadvantage is thatmanually selecting the correct reagent requires operator attention andaccuracy and there is an increased possibility of reagent applicationerrors, resulting in a decrease in test accuracy and operationalefficiency.

BRIEF DESCRIPTION OF THE DRAWINGS

The embodiments of the invention are illustrated by way of example andnot by way of limitation in the figures of the accompanying drawings inwhich like references indicate similar elements. It should be noted thatreferences to “an” or “one” embodiment in this disclosure are notnecessarily to the same embodiment, and such references mean at leastone.

FIG. 1 illustrates a perspective view of an embodiment of a sampleprocessing system.

FIG. 2 illustrates a perspective view of an embodiment of a sampleprocessing system with reaction stations.

FIG. 3A illustrates a perspective view of an embodiment of a reactionchamber.

FIG. 3B illustrates a side view of the reaction chamber of FIG. 3A.

FIG. 4A illustrates a perspective view of an embodiment of a reactionchamber and reagent cartridge of a sample processing system.

FIG. 4B illustrates a perspective view of an embodiment of a reactionchamber and reagent cartridge of a sample processing system.

FIG. 5A illustrates a perspective view of an embodiment of a reactionchamber.

FIG. 5B illustrates a side perspective view of an embodiment of areaction chamber.

FIG. 6A illustrates a perspective view of an embodiment of a reactionchamber.

FIG. 6B illustrates a perspective view of an embodiment of a reactionchamber.

FIG. 7 illustrates a top perspective view of an embodiment of a reagentcartridge.

FIG. 8 illustrates a bottom perspective view of the reagent cartridge ofFIG. 7.

FIG. 9A illustrates a perspective view of an embodiment of a reagentdispensing capsule and bracket.

FIG. 9B illustrates a perspective view of the reagent dispensing capsuleand bracket of FIG. 9A.

FIG. 10A illustrates a cross sectional side view of an embodiment of acapsule pressing mechanism during operation.

FIG. 10B illustrates a cross sectional side view of an embodiment of acapsule pressing mechanism during operation.

FIG. 10C illustrates a cross sectional side view of an embodiment of acapsule pressing mechanism during operation.

FIG. 10D illustrates a cross sectional side view of an embodiment of acapsule pressing mechanism during operation.

FIG. 11 is a perspective view of an embodiment of a reaction station ofa sample processing system.

FIG. 12 illustrates a perspective view of an embodiment of a temperaturemodifying assembly.

FIG. 13 illustrates a perspective view of an embodiment of an entirereaction station.

FIG. 14 illustrates a front perspective view of an embodiment of aninterlock assembly.

FIG. 15 illustrates a perspective view of an embodiment of an overheadfluid dispensing system and capsule pressing mechanism.

FIG. 16A illustrates a perspective view of an embodiment of an overheadfluid dispensing system.

FIG. 16B illustrates a perspective view of an embodiment of an overheadfluid dispensing system.

FIG. 17 illustrates a top view of an embodiment of a bulk fluiddispensing assembly.

FIG. 18 illustrates a top view of an embodiment of a fluid dispensingsystem.

FIG. 19 illustrates a schematic diagram of an embodiment of a sampleprocessing system including a bulk reagent sensing assembly.

FIG. 20 is an illustration of an embodiment of an automated sampleprocessing system.

FIG. 21 illustrates a flow chart of an embodiment of a sample processingprocedure.

FIG. 22 illustrates a flow chart of an embodiment of a sample processingprocedure.

FIG. 23 illustrates an embodiment of a display associated with a sampleprocessing procedure.

FIG. 24 illustrates an embodiment of a display associated with a sampleprocessing procedure.

FIG. 25A illustrates a perspective view of an embodiment of a wastedrain system of the sample processing system.

FIG. 25B illustrates a side view of the waste drain system of FIG. 25A.

FIG. 25C illustrates a back side view of the waste drain system of FIG.25A.

DETAILED DESCRIPTION

In the following paragraphs, the present invention will be described indetail by way of example with reference to the accompanying drawings.Throughout this description, the preferred embodiments and examplesshown should be considered as exemplars, rather than as limitations onthe present invention. Furthermore, reference to various aspects of theembodiments disclosed herein does not mean that all claimed embodimentsor methods must include the referenced aspects.

FIG. 1 illustrates a perspective view of an embodiment of a sampleprocessing system. Sample processing system 100 includes housing 102 forenclosing and storing various components of processing system 100.Housing 102 includes reaction compartment 104 and storage compartment106. Reaction compartment 104 defines a compartment within which sampleprocessing occurs. Cover member 108 and door member 110 may be used togain access to components within reaction compartment 104.

Reaction compartment 104 is dimensioned to accommodate a plurality ofreaction stations 112. Reaction stations 112 may slide in and out ofreaction compartment 104 to facilitate access to reaction chambers 114mounted thereon. In some embodiments, 30 reaction stations 112 arelinearly positioned within reaction compartment 104. In otherembodiments, reaction stations 112 are arranged in rows within reactioncompartment 104. For example, where 30 reaction stations 112 areprovided, each row may include 15 reaction stations 112. Although 30reaction stations 112 are described, it is contemplated that any numberof reaction stations 112 may be positioned within reaction compartment104 as deemed desirable.

Each of reaction stations 112 includes one of reaction chambers 114mounted thereon. Reaction chambers 114 are dimensioned to support aslide for further processing. A biological sample may be mounted to theslide for processing. During processing, a stain or other processingfluid is applied to the sample. In some embodiments, the processingfluid may be applied to the sample by a reagent cartridge attacheddirectly to each of reaction stations 112. In other embodiments, sampleprocessing system 100 may include a movable mounting assembly 116 formounting of fluid dispensing cartridges (not shown) above reactionstations 112. The fluid dispensing cartridges may include a fluid suchas a reagent that is to be applied to the sample. In addition, bulkcontainers 118 may be mounted below reaction stations 112. Bulkcontainers 118 may be reagent containers, waste containers or any otherbulk container found desirable. A reagent from bulk containers 118 mayfurther be dispensed onto the sample during processing.

System 100 may further include air inlet assembly 120 and air outletassembly 122 to help control a temperature within reaction compartment104. Processing of the samples within reaction compartment 104 generatesheat. As the temperature within reaction compartment 104 increases, sotoo does the rate of evaporation of any processing fluids used at thereaction stations. In addition, the increased temperature may have anegative impact on reagent stability. To help maintain a desiredtemperature within reaction compartment 104 (i.e. a temperature thatwill not speed up evaporation), air inlet assembly 120 and air outletassembly 122 may be used to circulate air through reaction compartment104. In this aspect, air inlet assembly 120 may include vent 124 mountedalong one side of a wall of housing 102 and one or more fans (not shown)mounted at an opposite side of the wall of housing 102 to help drawambient air into reaction compartment 104. Air outlet assembly 122 maybe mounted to a wall on an opposite side of housing 102 and include oneor more fans 126 coupled to an air outlet vent formed through the wallto help draw air out of reaction compartment 104. It is furthercontemplated that filters may be incorporated into air inlet assembly120 and/or air outlet assembly 122 to prevent contaminants from enteringreaction compartment 104. Circulating ambient air through reactioncompartment 104 as described helps to maintain a desired processingtemperature within reaction compartment 104.

FIG. 2 illustrates a perspective view of an embodiment of a sampleprocessing system with reaction stations. Processing system 200 includesreaction stations 202. Any number of reaction stations 202 may bepositioned within processing system 200. For example, in one embodiment,30 reaction stations 202 may be positioned within processing system 200.Each of reaction stations 202 may be independent from another. In thisaspect, each of reaction stations 202 may slide in and out of processingsystem 200 separately so that a user may easily access a desired one ofreaction stations 202 (e.g., see FIG. 1 with one reaction station 112slid partially out of processing system 100).

Each of reaction stations 202 of sample processing system 200 mayinclude support member 204. Support member 204 may be mounted to anupper surface of reaction station 202. Support member 204 may bedimensioned to support reaction chamber 206 and reagent cartridge 208.As previously discussed, reaction chamber 206 is dimensioned to supporta slide having a biological sample mounted thereon. A fluid may becaused to flow into reaction chamber 206 by virtue of one or acombination of capillarity (i.e., capillary action) (such as where thefluid enters a section in which the slide is positioned adjacentreaction chamber 206), pressure differential applied by an inlet oroutlet port of reaction chamber 206, vacuum pulsing and a fixed quantitypump, such as applied via one of the ports, and gravity (such as wherethe fluid flows from reagent cartridge 208 positioned above reactionchamber 206).

Reagent cartridge 208 may contain a primary reagent that is to beapplied to the slide having a sample mounted thereon. Representatively,reagent cartridge 208 may contain reagents suitable for a potentiallyunlimited variety of procedures, including immunohistochemistryprocedures, staining procedures, in situ hybridization procedures, otherhistochemical procedures etc. Examples of primary reagents (also calledprobes, markers or controls) that can be contained within reagentcartridge 208 include, without limitation, any type of antibodies,probes, nucleic acids (RNA, DNA or oligonucleotides), ligands, ligandreceptors, enzymes or enzyme substrates or any other molecules suitablefor a desired use. The reagents can be in a natural form, purified,concentrated, diluted or otherwise conditioned. In an embodiment, theaddition of signal molecules such as fluorescent dyes, enzymes,conjugates (e.g., biotin, avidin, streptavidin), metals (such as silveror gold particles), dyes, stains, radioactively tagged molecules, or anyother substances such as signaling or reporter molecules.

Reagent cartridge 208 may further be used to facilitate application ofone or more secondary reagents onto the slide. In one embodiment,secondary reagents are dispensed from above onto a drip and flow surfaceof reagent cartridge 208, for example by a fluid dispensing cartridge,as discussed in greater detail below. Examples of secondary reagentsthat can be dispensed onto the slide, either alone or in combinationwith other secondary reagents, or in combination with one or moreprimary reagents or bulk reagents include, without limitation, any typeof antibodies, probes, nucleic acids (RNA, DNA or oligonucleotides),ligands, ligand receptors, enzymes or enzyme substrates or any othermolecules suitable for a desired use. The reagents can be in a naturalform, purified, concentrated, diluted or otherwise conditioned. Inaddition, signal molecules such as fluorescent dyes, enzymes, conjugates(e.g., biotin, avidin, streptavidin), metals (such as silver or goldparticles), dyes, stains radioactively tagged molecules, or any othersubstances such as signaling or reporter molecules may also bedispensed.

In still further embodiments, one or more of a bulk type of reagent canbe applied to a slide positioned on reaction chamber 206. In someembodiments, bulk reagents are stored in containers and dispensed intoreaction chamber 206 via a manifold system directing the fluids into anentry port of reaction chamber 206. In addition, bulk reagents can bedispensed from an overhead bulk reagent dispenser onto reaction chamber206 via reagent cartridge 208 attached thereto. In still furtherembodiments, bulk reagents can be dispensed from reagent reservoir 210onto reaction chamber 206 via plumbing including a pump incorporatedinto reaction station 202. Examples of bulk reagents that can bedispensed either alone or in combination with other bulk reagents, or incombination with one or more primary reagents or secondary reagentsinclude, without limitation, the following: Tris Buffered Saline (TBS),distilled water or dewaxing solution.

FIG. 3A illustrates a perspective view of one embodiment of a reactionchamber. Reaction chamber 300 may be a tray dimensioned to retain asample and/or slide. As used herein the terms reaction chamber, sampleretaining tray and slide retaining tray are used interchangeably forreaction chamber 300. In the illustrated embodiment, reaction chamber300 is configured to be a microscope slide retaining tray but it shallbe appreciated that reaction chamber 300 is not so limited and may beconfigured to retain any sample or sample container. In accordance withan aspect of the embodiment, reaction chamber 300 functions as a slidepositioning and retention system that may be used in processing asubstrate such as a tissue sample.

In one embodiment, reaction chamber 300 can be used multiple times. Inother embodiments, reaction chamber 300 may be disposable. Reactionchamber 300 can be formed of a material having sufficient structuralstrength and process neutral properties to support a slide, retain andbe compatible with reagents and the temperatures employed during use.Representatively, in one embodiment, reaction chamber 300 may be made ofa hydrophilic material to facilitate capillary action as will bediscussed in more detail below and have a hardness sufficient towithstand scratching by glass slides placed thereon. In one embodiment,reaction chamber 300 may be made of a metal material. For example,reaction chamber 300 may be made of silver, steel or aluminum. A silvermaterial may be used to impart antimicrobial properties to reactionchamber 300. In the case of an aluminum reaction chamber 300, thesurface of the aluminum may be anodized to create a hydrophilic surface.A hydrophilic surface facilitates capillary action of a fluid betweenthe slide and reaction chamber 300. In some embodiments, the anodizedsurface may be thick, for example greater than 10 μm, still further,between about 10 μm and about 35 μm, for example, about 30 μm. Inaddition to rendering the surface hydrophilic, it is recognized that theanodized surface may increase corrosion resistance and wear resistanceof reaction chamber 300.

Other exemplary materials of reaction chamber 300 may includeheat-transferable polymeric materials such as plastics or cellulosic(i.e., cellulose based or comprising) materials, ceramic, Teflon®, glassetc. Representatively, reaction chamber 300 may be made of apolyoxymethylene thermoplastic such as DELRIN (a registered trademark ofE.I. DuPont de Nemours and Co. of Wilmington, Del.). Reaction chamber300 can be formed by any process known in the art such as injectionmolding, machining or any other manufacturing process suitable forgenerating the desired features of reaction chamber 300. In addition, itshould be appreciated that reaction chamber 300 can be composed of morethan one of the above discussed materials.

Reaction chamber 300 can optionally include an identifier that is humanor machine readable. Representative identifiers may include, but are notlimited to, visually readable, magnetically readable, tactilelyreadable, etc. identifiers. In some embodiments, the identifieridentifies a reagent to be used in connection with a slide positioned onreaction chamber 300, for example a primary reagent. In still furtherembodiments, the identifier identifies the sample within reactionchamber 300 or a processing protocol to be performed on the sample.

Specific features of reaction chamber 300 may include platen 302. Platen302 may be a substantially planar surface dimensioned to support slide322 thereon. Slide 322 may have a length dimension of 75 millimeters(mm) and a width dimension of 25 mm and a thickness of 1 mm. Processingof the sample (e.g. biological specimen) on slide 322 may take placebetween slide 322 and platen 302. In this aspect, slide 322 may bepositioned on platen 302 so that a surface of slide 322 containing thespecimen faces platen 302. Platen 302 may be dimensioned so that anentire processing area of the slide (i.e. unfrosted slide area) ispositioned on platen 302. In this aspect, where a sample occupies theentire slide processing area, the entire sample may be processed. Platen302 may include drip surface 330 at one end for receiving a reagentapplied to platen 302 from above. An opposite end of platen 302 mayinclude cut out portion 332 to facilitate grasping of slide 322positioned on platen 302.

Fluid inlet port 316 may be formed through platen 302 along a lengthdimension for applying a fluid to platen 302 from below (e.g. from abulk reagent reservoir). Fluid outlet ports 312, 314 may further beformed through platen 302 to facilitate removal of fluids from platen302. Fluid may be supplied or removed from platen 302 using fluid inletport 316 or fluid outlet ports 312, 314 via a fluid delivery system suchas a manifold and plumbing including passageways, a pump and valvespositioned below reaction chamber 300.

Wall 304 may be formed around a portion of platen 302 to help retain aprocessing fluid applied to platen 302. As illustrated in FIG. 3A, wall304 is formed around the ends and one side forming a length dimension ofplaten 302. It is contemplated, however, that wall 304 may be formedaround any portions of platen 302 necessary to facilitate retention of aprocessing fluid. Wall 304 may have a height sufficient to retain fluidsthat may pool within a corner of platen 302 and adjacent wall 304.Representatively, wall 304 should have a height sufficient to retainfrom about 25 microliters (μl) to about 200 μl in reaction chamber 300,representatively from about 25 μl to about 35 μl. In this aspect, wall304 may have a height of from about 4 mm to about 7 mm, for example,from 4.8 mm to 6.5 mm.

Wall 304 may form bend 328 along an end of platen 302 having reagentdrip surface 330. Bend 328 defines angle 334 along the end of platen 302to help direct a fluid dispensed onto reagent drip surface 330 along theend of platen 302 and between slide 322 and platen 302. Angle 334 ofbend 328 not only helps to direct the fluid toward slide 322 but furtherhelps to slow the flow of a fluid dispensed onto reagent drip surface330 of platen 302 so that the fluid does not flow over the top of slide322. Representatively, angle 334 may be from about 15 degrees to about35 degrees, preferably from about 20 degrees to about 30 degrees. In oneembodiment where reaction chamber 300 is configured to contain a slide(e.g., a microscope slide), drip surface 330 has a length dimension (11)on the order of 10.5 mm and a width dimension (w1) of 13 mm, and a widthdimension (w2) of 7.8 mm.

Wall 304 may also include protrusion 320 to help distance slide 322 fromwall 304. Spacing slide 322 a distance from wall 304 helps withintroducing and draining of fluids between slide 322 and platen 302. Inparticular, if the edge of slide 322 is flush with the portion of wall304 near the point of fluid introduction (e.g. reagent drip surface330), the fluid cannot flow freely along the edge of slide 322 andcapillary action cannot draw the fluid under the edge of slide 322. Inthis aspect, protrusion 320 may be dimensioned to space slide 322 adistance of from about 1 mm to about 2 mm, for example 1.5 mm, from wall304.

Reaction chamber 300 may further include spacer nodules 306, 308 andspacer bar 310 to facilitate fluid movement between slide 322 and platen302. Spacer nodules 306, 308 and spacer bar 310 may extend from asurface of platen 302 and create a gap between platen 302 and slide 322.The gap allows fluids (e.g. a reagent dispensed onto platen 302) to bedrawn between slide 322 and platen 302 by capillary action. It is to beunderstood that the smaller the gap, the greater the capillary action.In this aspect, in some embodiments, spacer nodules 306, 308 have aheight different from a height of spacer bar 310. This height differencecauses slide 322 to be supported at an angle with respect to platen 302.Capillary action is therefore stronger near the end of slide 322 closestto platen 302 then the other.

Representatively, a height of spacer nodules 306, 308 may be greaterthan a height of spacer bar 310 so that a gap near an end of slide 322where a fluid is applied from above reaction chamber 300 will be larger.In this aspect, a large volume of fluid may be applied to platen 302 atdrip surface 330 and initially drawn between the slide and platen 302 bycapillary action. The decrease in gap height towards the opposite end ofslide 322 (opposite from drip surface 330) will help draw the fluidacross the entire surface of slide 322. This gap further helps to draw afluid introduced through fluid inlet port 316 of platen 302 across anentire surface of slide 322. In other embodiments, spacer nodules 306,308 and spacer bar 310 may have the same height. It is noted that theheight may be adjusted depending upon the desired capillary action. Forexample, where a greater capillary force is desired, the height ofspacer nodules 306, 308 and/or spacer bar 310, may be decreased in orderto increase the capillary force.

Fluid inlet port 316 may be used to introduce a fluid directly betweenslide 322 and platen 302. Fluid outlet ports 312, 314 may be used todrain a fluid between slide 322 and platen 302. In some embodiments,fluid outlet ports 312, 314 and fluid inlet port 316 are positionedalong one side of the length dimension of platen 302. Fluid inlet port316 may be between fluid outlet ports 312, 314. The positioning of fluidoutlet ports 312, 314 and fluid inlet port 316 is important forcontrolling the dispersion of fluids between slide 322 and platen 302.Representatively, it is preferred that outlet ports 312, 314 be asufficient distance from their respective edges of platen 302 so as notto suck air from along the edge of slide 322. In addition, it ispreferred that at least one of outlet ports 312, 314 is within an areaof high surface tension (e.g. near spacer bar 310) so that an optimalamount of fluid may be withdrawn. In addition, it is preferred thatoutlet ports 312, 314 are positioned at opposite ends of platen 302 sothat fluids can be withdrawn across a length of platen 302 atsubstantially the same rate. This is in comparison to the funnelingeffect that would occur if fluid was removed through a single outletport positioned at, for example, the middle of platen 302. Funneling ofthe fluid into a single outlet port is not desirable because it resultsin large areas of the slide and platen 302 drying out. Although onefluid inlet port 316 and two fluid outlet ports 312, 314 are illustratedin FIG. 3A, it is contemplated that any number of outlet and inlet portsmay be formed through platen 302 depending upon, for example, thedesired fluid dispersion and/or platen 302 size. Further detailsregarding the dispersion of fluid between slide 322 and platen 302 willbe discussed in reference to FIG. 6A and FIG. 6B.

In some embodiments, reaction chamber 300 may be positioned withincasing 318. Casing 318 may be dimensioned to attach to the bottomportion of platen 302 and/or wall 304. Casing 318 may be used to helpseal reaction chamber 300 to an underlying support member (e.g. supportmember 404 illustrated in FIG. 4A) and prevent reagent leakage belowreaction chamber 300. Casing 318 may be made of the same or differentmaterial than reaction chamber 300. Representatively, in someembodiments, casing 318 may be made of a silicon material, or any othersimilar material, suitable for creating a seal between reaction chamber300 and the support member (e.g. support member 404 illustrated in FIG.4A).

FIG. 3B illustrates a side view of the reaction chamber of FIG. 3A. Ascan be seen from FIG. 3B, height, h1, of spacer nodule 308 may begreater than height, h2, of spacer bar 310. In this aspect, slide 322 ispositioned at an angle with respect to platen 302. Gap 324 formedbetween slide 322 and platen 302 is therefore greater at one end thananother. In some embodiments gap 324 is greater between an end of slide322 and platen 302 where fluid 326 is introduced (e.g. near reagent dripsurface 330). Representatively, in one embodiment, height, h1, of spacernodule 308 may be approximately 0.23 millimeters (mm) and height, h2, ofspacer bar 310 may be approximately 0.18 mm. In still furtherembodiments, height, h1, may be from about 0.15 mm to about 0.3 mm andheight, h2, may be from about 0.1 mm to about 0.25 mm.

Spacer nodule 308 may have any shape and dimensions sufficient to createa gap between slide 322 and platen 302. Representatively, spacer nodule308 may have a substantially square shape. Spacer nodule 306 may have asubstantially similar shape.

Spacer bar 310 may have any shape and dimensions sufficient to create agap between slide 322 and platen 302 and further to prevent flow of aliquid past spacer bar 310. In one embodiment, spacer bar 310 may havean elongated rectangular shape with a width dimension, w. It isimportant that spacer bar 310 have a length and width, w, sufficient toprevent a fluid between slide 322 and platen 302 from passing beyondspacer bar 310. In this aspect, spacer bar 310 has a length dimensionequal to a width of platen 302. A width, w, of spacer bar 310 may befrom about 1 mm to about 3 mm, preferably about 2 mm. In addition toblocking fluid flow, spacer bar 310 helps to eliminate air bubblesbetween platen 302 and slide 322 by directing air bubbles toward an edgeof slide 322. As will be discussed in more detail in reference to FIGS.5A and 5B, platen 302 may be positioned at an angle such that platen 302has a vertical and horizontal slant. In this aspect, a side of platen302 at one end of spacer bar 310 may be higher than a side of platen 302at the opposite end of spacer bar 310. Air bubbles trapped betweenplaten 302 and slide 322 will want to rise toward the higher side ofplaten 302. Spacer bar 310 can help to guide any air bubbles toward thehigher side and out from between slide 322 and platen 302.

FIGS. 4A and 4B illustrate a perspective view of a reaction chamber andreagent cartridge of a sample processing system. Sample processingsystem 400 includes support member 404 for supporting reaction chamber406 and reagent cartridge 408. Support member 404 is fixedly attached toa reaction station of system 400 and includes lower portion 410 andupper portion 412. Lower portion 410 is dimensioned to support reactionchamber 406 at horizontal and vertical angles as will be discussed inmore detail below. Reaction chamber 406 may be fixedly mounted to lowerportion 410. Upper portion 412 is dimensioned to support reagentcartridge 408 above a reagent drip surface of reaction chamber 406.Reagent cartridge 408 may be removably attached to upper portion 412 sothat reagent cartridge 408 may be removed and/or replaced as desired bya user. A reagent contained within reagent cartridge 408 or applied toreagent cartridge 408 may flow through reagent cartridge 408 and ontoreaction chamber 406.

In some embodiments, lower portion 410 and upper portion 412 may beintegrally formed pieces which form a substantially Z shaped profile.Support member 404 may be formed of any material having a sufficientstrength to support reaction chamber 406 and reagent cartridge 408 andprocessing within reaction chamber 406. Representatively, support member404 may be made of a metal or plastic material. Support member 404 canbe formed by any process known in the art such as injection molding,machining or any other manufacturing process suitable for generating thedesired features of support member 404.

Reaction chamber 406 may be substantially the same as reaction chamber300 described in reference to FIG. 3A. Slide 422 may be positioned onreaction chamber 406 as illustrated in FIG. 4A. During operation, areagent is dispensed from reagent cartridge 408 onto the reagent dripsurface (see reagent drip surface 330 illustrated in FIG. 3A) ofreaction chamber 406. Capillary action causes flow of reagent betweenslide 422 and platen 402.

FIG. 4B illustrates further details of reagent cartridge 408 previouslydiscussed in reference to FIG. 4A. Reagent cartridge 408 may be acartridge that contains a reagent or other processing fluid to beapplied to slide 422. In this aspect, reagent cartridge 408 may includereagent recess 414. Reagent recess 414 may be of any shape, depth ororientation as desired such that reagent(s) contained therein aredirected into reaction chamber 406. In one embodiment, the reagent iscontained within capsule 416 inserted within reagent recess 414. Wherecapsule 416 is cylindrical in shape, reagent recess 414 may furtherinclude a cylindrical shape. Reagent recess 414 includes an open bottomsuch that it is in fluid communication with outlet channel 418 extendingfrom a bottom of reagent cartridge 408. When capsule 416 within reagentrecess 414 is punctured, a reagent (e.g., liquid reagent) within capsule416 is expelled into reagent recess 414 and down through outlet channel418 onto a drip surface of reaction chamber 406 where it flows to platen402.

Reagent cartridge 408 may further help to direct a fluid dispensed froman overhead fluid dispensing cartridge onto a drip surface of reactionchamber 406. In this aspect, reagent cartridge 408 may include channel420 in fluid communication with outlet channel 418. Channel 420 extendsfrom a top surface of reagent cartridge 408 through reagent cartridge408 to outlet channel 418. A fluid (e.g. a reagent) dispensed intochannel 420 from an overhead fluid dispenser travels through reagentcartridge 408 and out outlet channel 418 onto reaction chamber 406.Since both channel 420 and reagent recess 414 are in fluid communicationwith outlet channel 418, fluids dispensed from each are mixed withinoutlet channel 418 prior to being dispensed onto reaction chamber 406.In this aspect, outlet channel 418 serves as a mixing chamber for two ormore fluids dispensed from reagent cartridge 408.

In some embodiments, two or more fluids may be dispensed into channel420 from an overhead fluid dispenser. In this aspect, channel 420 mayhave a width dimension (w1) sufficient to receive two or more fluids.Representatively, channel 420 may have a width of from about 10 mm toabout 15 mm, preferably about 12.5 mm. In addition, it is contemplatedthat a shape of the bottom of channel 420 may have an unreflecting curveto minimize splashing of fluids dispensed into channel 420.

Capsule 416 may be attached to reagent cartridge 408 with bracket 424.Bracket 424 may include an elongated connector 426 such as a strap whichattaches to capsule 416. In one embodiment, capsule 416 is removablyattached to connector 426 of bracket 424. In other embodiments, capsule416 is fixedly attached to connector 426. Reagent cartridge 408 mayinclude indentation 430 dimensioned to receive bracket 424. In addition,furrow 432 may be formed within reagent cartridge 408 betweenindentation 430 and reagent recess 414. Connector 426 may be insertedwithin furrow 432 when bracket 424 is attached to reagent cartridge 408so that capsule 416 is securely aligned within reagent recess 414 by areaction force of connector 426.

Identifier 428 may be placed on bracket 424 as illustrated in FIG. 4B.Identifier 428 will be discussed in more detail in reference to FIG. 9A.Reagent cartridge 408 and capsule 416 will be discussed in more detailin reference to FIGS. 7-9.

Reagent cartridge 408 may be made of the same or different material asreaction chamber 406. Representatively, reagent cartridge 408 may bemade of a plastic, metal or ceramic material and formed by any processknown in the art such as injection molding, machining or any othermanufacturing process suitable for generating the desired features.

FIGS. 5A and 5B are perspective views illustrating the horizontal andvertical angles of one embodiment of a reaction chamber. Reactionchamber 506 is positioned at horizontal angle 534 and vertical angle 536to facilitate movement of fluid (e.g. reagent) between slide 522 andplaten 502. FIGS. 5A and 5B illustrate reaction chamber 506 positionedon lower portion 510 of support member 504. Lower portion 510 isdimensioned to receive and position reaction chamber 506 at horizontalangle 534 and vertical angle 536. Horizontal angle 534 refers to theangle of an edge of reaction chamber 506 defining a length dimension ofreaction chamber 506 with respect to the level ground. Vertical angle536 refers to the angle of a surface of reaction chamber 506 definingplaten 502 to the level ground. Horizontal angle 534 is illustrated inFIG. 5A and vertical angle 536 is illustrated in FIG. 5B. Horizontalangle 534 may be from about 5 degrees to about 15 degrees, for examplefrom 6 degrees to 8 degrees, and in another example, about 7 degrees.Vertical angle 536 may be from about 15 degrees to about 45 degrees, forexample from 20 degrees to 30 degrees, and in another example, about 29degrees.

As previously discussed, horizontal angle 534 and vertical angle 536 ofreaction chamber 506 help to direct fluid dispersion or movement betweenplaten 502 and slide 522. In particular, vertical angle 536 causes edge538 of platen 502 forming the length dimension and adjacent reagent dripsurface 530 to be positioned higher than an opposite edge 540 of platen502. Horizontal angle 534 causes end 542 of platen adjacent reagent dripsurface 530 to be positioned lower than opposite end 544 of platen 502.Since corner 546 of platen 502 is higher than the diagonally opposedcorner 548, air bubbles trapped between slide 522 and platen 502 canrise toward the higher edge/end of slide 522 and escape. In addition,when a fluid (e.g. reagent) is dispensed onto reagent drip surface 530,gravity draws the fluid downward toward the corner 548 of platen 502. Asthe fluid flows toward corner 548, it flows along end 542 of platen andthe adjacent end of slide 522 and is drawn between slide 522 and platen502 by capillary action. Once the fluid is between slide 522 and platen502, capillary action further draws the fluid against gravity along thelength of slide 522 toward the upper most corner 546 of platen 502.

Horizontal angle 534 of platen 502 also facilitates draining of reactionchamber 506 by preventing fluid from pooling along the bottom edge ofslide 522. Instead, the fluid is drawn toward bottom corner 548 ofplaten 502 where a fluid outlet port is positioned so that the fluid canbe removed through the outlet port. In addition, any overflow fluids arecontained along bottom corner 548, preventing them from flowing over thetop of slide 522.

FIGS. 6A and 6B illustrate a perspective view of one embodiment of areaction chamber. Reaction chamber 600 may be substantially the same asreaction chamber 300 described in reference to FIG. 3A. Reaction chamber600 may include platen 602 dimensioned to support slide 622 thereon.Platen 602 may include reagent drip surface 630 at one end for receivinga reagent applied to platen 602 from above. An opposite end of platen602 may include cut out portion 632 to facilitate grasping of slide 622positioned on platen 602.

Wall 604 may be formed around a portion of platen 602 to retain areagent placed on platen 602. Wall 604 may have a height sufficient toretain fluids that may pool within a corner formed by platen 602 andwall 604. Wall 604 may form bend 628 having angle 634 along an end ofplaten 602. Wall 604 may also include protrusion 620 to help distanceslide 622 from wall 604.

Spacer nodules 606, 608 and spacer bar 610 may extend from a surface ofplaten 602 and create a gap between platen 602 and slide 622. Fluidoutlet ports 612, 614 and fluid inlet port 616 may be formed throughplaten 602.

FIG. 6A illustrates a flow path of fluid between slide 622 and platen602 when fluid is introduced from a fluid dispensing cartridgepositioned above reaction chamber 600. In particular, the fluid (e.g.reagent) may be dispensed onto reagent drip surface 630. Due to thehorizontal and vertical angles of reaction chamber 300 as well as bend628 of wall 604 as previously discussed, the fluid follows flow path 640along bend 628 of wall 604 and an edge of slide 622. Bend 628 of wall604 provides a slope (angle 634) which slows the flow of the fluidflowing from reagent drip surface 630 toward slide 622. In particular,in the absence of bend 628, fluid would flow directly from reagent dripsurface 630 down the edge of slide 622. Such a large amount of fluidwould flow at such a speed that some of the fluid would flow over a sideof slide 622 opposite platen 602. Angle 634 of bend 628 of wall 604 andthe horizontal and vertical angles of reaction chamber 600 help to slowthe fluid down and spread it along the edge of slide 622 to prevent suchoverflow.

Some of the fluid continues along wall 604 to the bottom corner of slide622 while some of the fluid is immediately drawn between slide 622 andplaten 602 by capillary action. The fluid that pools between wall 604and the bottom corner of slide 622 is also drawn between slide 622 andplaten 602 by capillary action. The fluid that is immediately drawnbetween slide 622 and platen 602 flows along flow path 640 a while thefluid that initially pools at the corner of slide 622 follows flow path640 b. Flow path 640 a and 640 b eventually converge to form a singlewave front 642 that travels across the length of slide 622 toward anopposite end of slide 622. Introducing the fluid between slide 622 andplaten 602 at two different points allows the fluid to cover asubstantial width of slide 622 across the entire length of slide 622. Inthis aspect, wave front 642 of the fluid is substantially even across anentire length of slide 622 thereby maximizing fluid coverage.

FIG. 6B illustrates a flow path of fluid between slide 622 and platen602 when fluid is introduced through fluid inlet port 616. Fluid inletport 616 is positioned off center with respect to a distance betweenspacer bar 610 and an opposite end of reaction chamber 600. Positioningof fluid inlet port 616 in this manner achieves a desired balancebetween the velocity with which the fluid introduced through fluid inletport 616 travels across slide 622, the fluid coverage and the amount ofair bubbles trapped between slide 622 and platen 602. In particular, ithas been found that when the fluid is introduced through an inlet portpositioned a greater distance from spacer bar 610 (e.g. 20 mm), thefluid travels across slide 622 at a slower speed and more air bubblesremain trapped between slide 622 and platen 602 then where fluid isintroduced through an inlet port positioned closer to spacer bar 610(e.g. 5 mm). Introducing the fluid at a slower speed (e.g. where inletport 616 is a greater distance from spacer bar 610) allows for a moreeven wave front to travel across the slide and therefore better slidecoverage. When the inlet port is positioned closer to spacer bar 610,the fluid flows at a higher velocity and there are fewer air bubbles butthe fluid fills starting from spacer bar 610 and continues across slide622 at an undesirable angle.

As illustrated in FIG. 6B, when fluid is introduced through inlet port616 positioned off center (e.g. 15 mm to about 20 mm from spacer bar610), fluid follows flow path 644 in a vertical direction across a widthof slide 622. Flow path 644 has a substantially even wave front 642allowing for optimal slide coverage.

FIG. 7 illustrates a top perspective view of an embodiment of a reagentcartridge. Reagent cartridge 700 is substantially the same as reagentcartridge 408 described in reference to FIG. 4B except that in thisembodiment the reagent capsule is removed so that features of reagentrecess 714 can be more clearly seen. In this aspect, reagent cartridge700 includes housing 702 which attaches to a support member such as thatdescribed in reference to FIG. 4A. Housing 702 includes reagent recess714, channel 720 and indentation 730. Reagent recess 714 and channel 720converge to form outlet channel 718.

As previously discussed, indentation 730 is dimensioned to receive abracket (see bracket 424 of FIG. 4B) that is connected to the reagentcapsule. FIG. 7 shows indentation 730 having slots 734, 736 dimensionedto receive bracket arms (see arms 922, 924 of FIG. 9A) extending from anunderside of the bracket. The bracket arms are inserted into slots 734,736 to position and hold the bracket on indentation 730 and, in turn,reagent capsule within reagent recess 714. Reagent recess 714 includesledge 738 formed within reagent recess 714 to support a reagent capsulepositioned therein. As can be seen from FIG. 7, ledge 738 extends fromthe wall of reagent recess 714 but does not close the opening of recess714 so as to allow a reagent dispensed from the capsule to travelthrough reagent recess 714 to outlet channel 718.

Housing 702 further defines furrow 732 extending between indentation 730and reagent recess 714. Furrow 732 is dimensioned to receive theconnector connecting the bracket to the reagent capsule as previouslydiscussed. Positioning of a bracket within indentation 730 and aconnector within furrow 732 facilitates alignment of the reagent capsulewithin recess 714.

FIG. 8 illustrates a bottom perspective view of the reagent cartridge ofFIG. 7. From this view it can be seen that tabs 840, 842 extend fromhousing 702 below slots 734, 736, respectively. Tabs 840, 842 aredimensioned to position and hold reagent cartridge 700 on the upperportion of the support member (see upper portion 412 of support member404 of FIG. 4A.) In this aspect, the support member may include slotswithin which tabs 840, 842 may be removably inserted. Tabs 840, 842, andin turn reagent cartridge 700, may be removed from the upper portion bypulling reagent cartridge in a direction away from the support member.

Slots 734, 736 may be dimensioned to receive arms extending from abottom side of the bracket as illustrated in FIG. 9B. In this aspect,slots 734, 736 help to secure the bracket to reagent cartridge 700. Thearms of the bracket may be removed from slots 734, 736 by pulling thebracket in a direction away from housing 702. Alternatively, the bracketmay snap fit within slots 734, 736 such that to release the bracket fromslots 734, 736.

Reagent recess 714 connects to outlet channel 718 via reagent recesschannel 846. Reagent recess channel 846 provides a sloped surface alongwhich a reagent from, for example, a capsule positioned within reagentrecess 714 can travel in a direction toward outlet channel 718. Reagentrecess channel 846 converges with channel 720.

Channel 720 includes first inclined portion 848 and second inclinedportion 850. First inclined portion 848 is at a slope of approximately30 degrees with respect to horizontal. Second inclined portion 850extends from first inclined portion at a right angle toward reagentrecess channel 846 and is further at a slope of approximately 30degrees. The dimensions of channel 720 and reagent recess channel 846are selected so that fluids traveling along the channels converge withone another and mix prior to being dispensed onto an underlying reactionchamber. In this aspect, multiple fluids may be mixed together anddispensed from outlet 844 of outlet channel 718. In addition, it ispreferred that the various flow paths of reagent cartridge 700 (e.g.recess channel 846, channel 720 and outlet channel 718) have a tubular,rounded dimension to inhibit trapping of fluids traveling through theflow paths and minimize splashing when fluid is dispensed within theflow paths.

FIG. 9A illustrates a perspective view of an embodiment of a reagentdispensing capsule and bracket. Capsule 900 includes container 902dimensioned to hold a reagent therein. Seal 930 may be positioned acrossthe opening of container 902 to retain the reagent. Within capsule 900is plunger 904. Plunger 904 may be an elongated structure having one endattached to the closed end of container 902 and an opposite endextending toward the opening of container 902. The end of plunger 904positioned at the opening of container 902 may be adapted for piercingthrough seal 930 formed across the opening of container 902.Representatively, the end of plunger 904 may have one or more spikesextending from the end. During operation, a force is applied to theclosed end of container 902 causing container 902 to collapse and pushplunger 904 in a direction of seal 930. Plunger 904 contacts andpunctures seal 930, thereby opening the end of container 902 to allowfor release of the reagent contained therein.

Reagent capsule 900 may be attached to bracket 910 by connector 906 aspreviously discussed. In this aspect, connector 906 may have attachmentend 908 which fits into receiving slot 916 formed by bracket 910.Bracket 910 may have top side 912 and back side 914 which are formed atright angles to one another. In this aspect, when bracket 910 isattached to the reagent cartridge (e.g. reagent cartridge 700 of FIG.7), top side 912 is positioned within the indentation (e.g. indentation730 of FIG. 7) formed along a top side of the reagent cartridge. Backside 914 of bracket 910 overlaps a back side of the reagent cartridge.

Identifiers 918, 920 may be positioned on bracket 910. Identifiers 918,920 may contain machine understandable codes, such as provided by radiofrequency identification (RFID) tags, shape identifiers, coloridentifiers, numbers or words, other optical codes, barcodes etc.Identifiers 918, 920 may be used to identify, for example, the contentsof capsule 902 and/or a processing protocol. Still further, one or moreof identifiers 918, 920 may contain patient information and history,information regarding biological sample(s) on the slides, arrival anddeparture times of biological samples, tests performed on the samples,diagnoses made and so on. Identifiers 918, 920 may contain the same ordifferent information.

In some embodiments, one or more of identifiers 918, 920 may beremovable so that the identifier can be attached to another article ofthe system. For example, identifier 918 may contain informationidentifying a reagent contained within capsule 902 and/or a processingprotocol. Identifier 920 may contain the same information. Prior toprocessing a slide using the contents (e.g. reagent) of capsule 902,identifier 918 may be removed from bracket 910 and positioned on theslide. Alternatively, identifier 918 can be positioned on the slideafter processing. The reagent and/or process performed on the slide canthen be readily determined from identifier 918 on the slide. The abilityto transfer identifiers in this manner helps to prevent processing andidentification errors.

FIG. 9B illustrates a perspective view of the reagent dispensing capsuleand the bracket of FIG. 9A. From this view, bracket arms 922, 924extending from a bottom surface of bracket 910 can be seen. When bracket910 is positioned within the indentation (e.g. indentation 730 of FIG.7) of the reagent cartridge (e.g. reagent cartridge 700 of FIG. 7),bracket arms 922, 924 fit within the slots (e.g. slots 734, 736 of FIG.7) formed in the indentation of the reagent cartridge to hold bracket910, and in turn, capsule 900, in place. Bracket arms 922, 924 catch onthe wall of the reagent cartridge forming slots 734, 736 (see FIG. 8),respectively to lock bracket 910 in place. In this aspect, bracket arms922, 924 may have any size or dimensions complimentary to slots 734, 736of reagent cartridge 700.

FIGS. 10A-10D illustrate a cross sectional side view of a capsulepressing mechanism during operation. FIG. 10A illustrates capsulepressing mechanism 1000 in a raised position such that it does notcontact the underlying reagent capsule 1024. Capsule pressing mechanism1000 includes housing 1002 for supporting components of pressingmechanism 1000. The components of pressing mechanism 1000 may includepiston 1004 having head member 1006 positioned at one end. Spring member1008 may further be positioned around an opposite end of piston 1004 tobias piston 1004 in a raised position.

Crank shaft 1010 may be attached to piston 1004 to drive verticalmovement of piston 1004. Crank shaft 1010 may be rotatably attached topiston 1004 at one end and gear 1012 at an opposite end. Gear 1012 maybe rotated by lateral movement of slide arm 1014. Slide arm 1014 mayinclude teeth along one side which are complimentary to the teeth ofgear 1012. Lateral movement of slide arm 1014 causes the teeth of slidearm 1014 to engage with the teeth of gear 1012 and rotate gear 1012 in aclockwise or counter clockwise direction. Rotation of gear 1012 in turncauses the end of crank shaft 1010 attached to piston 1004 to movevertically. When the end of crank shaft 1010 moves in an upwarddirection, piston 1004 is raised and when crank shaft 1010 moves in adownward direction, piston 1004 is lowered. Lateral movement of slidearm 1014 may be driven by actuator 1016. Actuator 1016 may be any typeof actuating mechanism capable of driving lateral movement of slide arm1014. Representatively, actuator 1016 may be a unit including a motorand a gear which may be engaged with a gear located on an opposite sideof slide arm 1014.

Reagent cartridge 1018 may be positioned below capsule pressingmechanism 1000. Reagent cartridge 1018 may be substantially the same asreagent cartridge 408 described in reference to FIG. 4B. In this aspect,reagent cartridge 1018 includes reagent recess 1022 for holding reagentcapsule 1024. Reagent cartridge 1018 further includes channel 1020.Reagent capsule 1024 includes container 1030 having one end sealed withseal 1026. Seal 1026 may be any type of seal capable of being puncturedby plunger 1028 to release contents within reagent capsule 1024.Representatively, seal 1026 may be a heat seal made of a metal foil orplastic material.

In some embodiments, breaking of seal 1026 and release of a reagent fromreagent capsule 1024 is accomplished by a two step process asillustrated by FIGS. 10B, 10C and 10D. In particular, during operation,pressing mechanism 1000 drives piston 1004 vertically in a directiontoward reagent capsule 1024. Head 1006 of piston 1004 presses on reagentcapsule 1024, collapsing capsule 1024 and driving plunger 1028 throughseal 1026 as illustrated in FIG. 10B. A stroke length of piston 1004 iscontrolled so that once seal 1026 is broken, vertical movement of piston1004 is reversed and piston 1004 is raised as illustrated in FIG. 10C.During the initial downward piston stroke, only a small amount ofreagent from capsule 1024 is released. Raising of piston 1004 allows asmall amount of air into capsule 1024. The downward vertical movement ofpiston 1004 is then recommenced and head 1006 of piston 1004 completelycollapses capsule 1024 causing ejection of the entire contents heldwithin capsule 1024 as illustrated in FIG. 10D.

It has been found that breaking of the seal and releasing the entirecontents of capsule 1024 with one stroke of piston 1004 causes some ofthe reagent held within capsule 1024 to splash out of capsule 1024resulting in loss of some of the reagent. Such splashing can be reducedor eliminated using a first piston stroke to puncture seal 1026,allowing some air to enter capsule 1024 and then a second piston stroketo eject the remaining contents of capsule 1024. Once all the reagent isejected from capsule 1024, piston 1004 is raised back to its initialposition as illustrated in FIG. 10A.

FIG. 11 is a perspective view of a reaction station of a sampleprocessing system. Reaction station 1100 includes support member 1102having reaction chamber 1104 and reagent cartridge 1106 positionedthereon. Support member 1102, reaction chamber 1104 and reagentcartridge 1106 may be substantially the same as support member 404,reaction chamber 406 and reagent cartridge 408 described in reference toFIG. 4A.

As can be seen from this view, reaction station 1100 further includesreservoir 1108. Reservoir 1108 may be used to hold a bulk reagent thatis to be supplied to reaction chamber 1104 during processing. In thisaspect, reservoir 1108 is attached to support member 1102 and is influid communication with reaction chamber 1104. Typically in sampleprocessing systems, there are several reagents that must be applied tothe reaction chamber at various times during processing. Such reagentsare normally contained in bulk containers and separate supply lines mustrun from the container to each reaction chamber. Reservoir 1108,however, eliminates the need for multiple supply lines. Instead, as willbe described in more detail in reference to FIG. 16A, FIG. 16B and FIG.17, supply lines from each bulk container run to a single bulkdispenser. The bulk dispenser may then be positioned over reservoir 1108to dispense the desired bulk reagent into reservoir 1108. Aliquots ofthe fluid contained within reservoir 1108 may then be removed andapplied to reaction chamber 1104 according to the processing protocol.Such configuration is particularly advantageous where multiple reactionchambers are present in the system because it allows the desired fluidto be applied to each reaction chamber at any time. This is in contrastto typical processing systems in which application of a fluid from thebulk container to one reaction chamber may be delayed until applicationof the fluid to another reaction chamber is completed.

Reservoir 1108 may have dimensions suitable for holding a volume ofliquid needed to complete processing within the reaction chamber 1104.For example, reservoir 1108 may hold a volume of, for example, up to 10ml, in some embodiments about 6 ml. Aliquots in the amount of, forexample, 500 microliters (μl), may be transferred from reservoir 1108 toreaction chamber 1104 at desired times during processing. A supply line(not shown) may run from reservoir 1108 to reaction chamber 1104 alongsupport member 1102 to transfer the fluid from reservoir 1108 toreaction chamber 1104.

Waste line 1110 may be connected to reservoir 1108. Waste line 1110 mayfacilitate removal of excess fluids from reservoir 1108 and/or changingof a fluid held within reservoir 1108.

Reaction station 1100 may further include a temperature modifyingassembly 1112 to heat and cool reaction chamber 1104. It is importantduring processing of a sample within reaction chamber 1104 that theplaten of reaction chamber 1104 is able to be heated and cooled asdesired. Rapid cooling is important during, for example, antigenretrieval, particularly after steps involving heating of reactionchamber 1104. In this aspect, temperature modifying assembly 1112 ispositioned below reaction chamber 1104. Temperature modifying assembly1112 may include a thermoelectric cooler (TEC) (see TEC 1206, 1204described in reference to FIG. 12), heat sink 1114 and fan 1116 as willbe discussed in more detail in reference to FIG. 12.

FIG. 12 illustrates a perspective view of one embodiment of atemperature modifying assembly. Temperature modifying assembly 1200 mayinclude reaction chamber 1202, TEC 1204 and 1206, heat sink 1208 and fan1214. TEC 1204 and 1206 may be positioned in a side by sideconfiguration along an underside of reaction chamber 1202. TEC 1204 and1206 may be used to either heat or cool reaction chamber 1202. To coolreaction chamber 1202, heat from a side of TEC 1204 and 1206 contactingreaction chamber 1202 is transferred to an opposite side of TEC 1204 and1206. To heat reaction chamber 1202, transfer of heat is reversed inthat it is transferred from the side of TEC 1204 and 1206 oppositereaction chamber 1202 to the side contacting reaction chamber 1202. TEC1204 and 1206 may be any TEC device such as that commercially availablefrom Ferrotec Corporation under the model number 9501/071/040BS/L300.

Heat sink 1208 and fan 1214 may facilitate heat transfer within TEC 1204and 1206. In particular, heat sink 1208 may include base portion 1210attached to a surface of TEC 1204 and 1206 and fin portion 1212. Baseportion 1210 may be a solid block made of a heat transferring material,for example, aluminum. In this aspect, base portion 1210 may be used toincrease a heat capacity of heat sink 1208. Fin portion 1212 extendsfrom base portion 1210. Heat from TEC 1204 and 1206 is absorbed by baseportion 1210 and dissipated into the air through fin portion 1212. TEC1204 and 1206 and heat sink 1208 allow for direct cooling and/or heatingof reaction chamber 1202.

Fan 1214 is positioned so that it blows air onto fin portion 1212 tofacilitate heat dissipation. A speed of fan 1214 may be fixed orcontrolled by a user and modified depending upon the level of heatdissipation desired. Representatively, where rapid cooling of TEC 1204and 1206, and in turn reaction chamber 1202, is desired, a speed of fan1214 may be increased in order to increase a circulation of airthroughout fin 1212. In this aspect, temperature modifying assembly 1200may be capable of rapidly cooling reaction chamber 1202 from atemperature of 98 degrees Celsius to 10 degrees Celsius within 5minutes, for example, in less than 3 minutes.

In some embodiments, temperature modifying assembly 1200 may furtherinclude one or more thermistors. Representatively, thermistors 1216 and1218 may be sandwiched between reaction chamber 1202 and TEC 1204 and1206, respectively. Thermistors 1216 and 1218 may be used for monitoringand/or controlling a temperature of temperature modifying assembly 1200.In particular, thermistors 1216 and 1218 may measure a temperature ofreaction chamber 1202. This temperature may be used to determine whethera temperature of TEC 1204 and 1206 should be maintained or modified.

FIG. 13 illustrates a perspective view of an embodiment of an entirereaction station. Reaction station 1300 includes a reaction stationsimilar to reaction station 1100 previously discussed in reference toFIG. 11 and includes temperature modifying assembly 1302 similar totemperature modifying assembly 1200 previously discussed in reference toFIG. 12. Reaction station 1300 includes support member 1304 havingreaction chamber 1306 and reagent cartridge 1308 positioned therein.Reaction station 1300 further includes reservoir 1310. A TEC device (notillustrated), heat sink 1314 and fan 1312 such as that previouslydiscussed in reference to FIG. 12 are positioned beneath reactionchamber 1306.

Reaction station 1300 further includes identification platform 1316 andhandle portion 1320. Identification platform 1316 is positioned at anend of reaction station 1300 that is viewable by a user. Identificationplatform 1316 may include identifier 1318 which identifies reactionstation 1300. As previously discussed, the sample processing system mayinclude more than one reaction station 1300 so that processing ofmultiple samples may occur at one time. It is therefore desirable toidentify each reaction station 1300 with identifier 1318 so that theuser and/or system can identify the reaction station processing aparticular sample and/or a location of the sample. Identifier 1318 maybe any of the previously discussed types of identifiers, for example,radio frequency identification (RFID) tags, shape identifiers, coloridentifiers, numbers or words, other optical codes, barcodes, etc.

As previously discussed in reference to FIG. 1, reaction station 1300may slide in and out of a reaction compartment (see reaction compartment104 illustrated in FIG. 1) formed by a housing (see housing 102illustrated in FIG. 1) to facilitate access to reaction chamber 1306mounted therein. Rail member 1322 may be connected to the housing andprovide a surface along which reaction station 1300 may slide.Representatively, rail member 1322 may include a channel to guidereaction station 1300 in and out of the reaction compartment. Handle1320 extending from an end of reaction station 1300 may be used to slidereaction station 1300 in and out of the reaction compartment.

Interlock assembly 1324 may be connected to an end of reaction station1300 opposite handle 1320. FIG. 13 illustrates a back side view ofinterlock assembly 1324. Interlock assembly 1324 may be any type ofinterlocking system capable of locking reaction station 1300 within thereaction compartment and preventing its removal. In some embodiments,interlock assembly 1324 may include an electromechanical locking system.Representatively, interlock assembly 1324 may include a bistablesolenoid. It is desirable that interlock assembly 1324 remains locked inthe event of a power failure in order to prevent improper removal ofreaction station 1300. Representatively, in the event of a powerfailure, interlock assembly 1324 remains in the locked position until auser purposely unlocks interlock assembly 1324. Interlock assembly 1324may serve as a secondary locking system for each individual reactionstation 1300 while a primary locking system may be provided for lockingthe system housing (e.g. cover member 108 and door member 110 ofreaction compartment 104 discussed in reference to FIG. 1). The primarylocking system may unlock the system in the event of a power failure toallow a user access to each reaction station 1300, however, removal ofreaction station 1300 may still be prevented by interlock assembly 1324.

FIG. 14 illustrates a front perspective view of the interlock assemblydescribed in reference to FIG. 13. Interlock assembly 1324 may includeelectromechanical locking system 1412. In some embodiments,electromechanical locking system 1412 may be a bistable solenoid such asthat available commercially from Takano Co., LTD under product numberTSB-0805-SS1. Frame member 1326 for supporting bistable solenoid 1412may be attached to rail member 1322 of the reaction compartment.Bistable solenoid 1412 may generally include solenoid housing 1414attached to frame member 1326. Thrust pin 1416 may extend from an upperend of housing 1414 and plunger 1418 may extend from a lower end ofhousing 1414. Thrust pin 1416 and plunger 1418 are connected and movesimultaneously in a vertical direction. Thrust pin 1416 is used forlocking or unlocking reaction station 1300 and plunger 1418 is used fordetecting locking or unlocking of reaction station 1300.

Lock arm 1328 of reaction station 1300 may include aperture 1420dimensioned to receive thrust pin 1416. Aperture 1420 is positionedwithin lock arm 1328 such that when reaction station sensor 1330 detectsthe presence of lock arm 1328, aperture 1420 is aligned with thrust pin1416. Thrust pin 1416 may then be advanced toward lock arm 1328 andthrough aperture 1420 to lock reaction station 1300 in place. Bistablesolenoid 1412 allows thrust pin 1416 to be held in the locked positioneven after power is disconnected. Where power is lost and unlocking ofinterlock assembly 1324 is desired, a tool may be used to dislodgethrust pin 1416 from within aperture 1420.

Reaction station sensor 1330 may be used to detect the presence ofreaction station 1330 within the reaction compartment. Reaction stationsensor 1330 including detection arms 1402 and 1404 is attached to framemember 1326. A space may be provided between detection arms 1402 and1404 on reaction station sensor 1330 for receiving lock arm 1328.Detection arms 1402 and 1404 may include sensor elements to detect thepresence or absence of lock arm 1328. Representatively, arm 1402 mayemit a laser beam toward a beam detector on arm 1404. When the laserbeam is interrupted by lock arm 1328, the detector on arm 1404 no longerdetects the beam from arm 1402. The system is then alerted that reactionstation 1300 is in position and may be locked in place. Similarly, whenthe laser beam is detected by the laser beam detector on arm 1404 (i.e.lock arm 1328 is not between arms 1402, 1404), interlock assembly 1324remains in the unlocked position. Reaction station sensor may include avariety of types of sensors and/or switches, including, but not limitedto, optical sensors and read switches.

Interlock sensor 1406 to detect the position (locked or unlocked) ofinterlock assembly 1324 may further be attached to frame member 1326.Similar to reaction station sensor 1330, interlock sensor 1406 mayinclude detection arms 1408 and 1410. Detection arm 1408 may include alaser beam directed toward a laser beam detector on arm 1410. In thisaspect, detection arms 1408 and 1410 can detect the position (lock orunlock) of interlock assembly 1324.

The reaction station position information obtained from reaction stationsensor 1330 and/or interlock sensor 1406 may be used to detect theintroduction of a new slide to the system during processing. Forexample, in an embodiment where there are 30 reaction stations 1300within the system, a user may initially position slides at 20 reactionstations 1300. The remaining 10 reaction stations may be empty. Each ofreaction stations 1300 are initially scanned to determine whether aslide and corresponding reagent cartridge are positioned thereon. Theappropriate processing protocols will then be performed at only stationshaving slides and reagent cartridges therein. If, during processing, auser wants to add a slide to one of the empty reaction stations, theuser opens the reaction chamber and slides an empty reaction stationout, places the slide and reagent cartridge on the station and thenslides it back in. The sensors detect that one of reaction stations 1300has been removed and slid back into a locked position. Based on thisinformation, the system then knows to scan the station and process thenew slide.

FIG. 15 illustrates a perspective view of one embodiment of an overheadfluid dispensing system and capsule pressing mechanism. Fluid dispensingsystem 1500 generally includes fluid dispensing assembly 1502 used todispense a fluid onto a reaction chamber of an underlying reactionstation. Fluid dispensing assembly 1502 is attached to mounting assembly1506. Capsule pressing mechanism 1504 for facilitating release of areagent from a reagent capsule within a reagent cartridge of reactionstation may further be attached to mounting assembly 1506. Fluiddispensing assembly 1502 and capsule pressing mechanism 1504 may bepositioned within mounting stations (see mounting stations 1618 of FIG.16A) of mounting assembly 1506. Although one fluid dispensing assembly1502 and capsule pressing mechanism 1504 are illustrated in FIG. 15, itis contemplated that any number of fluid dispensing assembly 1502 andcapsules pressing mechanism 1504 may be mounted to mounting assembly1506. Representatively, in one embodiment, mounting assembly 1506 mayinclude at least 20 mounting stations having at least 19 fluiddispensing assemblies 1502 and at least one capsule pressing mechanism1504 mounted thereto. In some embodiments which have two capsulepressing mechanisms, capsule pressing mechanism 1504 may be mounted at aside of mounting assembly 1506 opposite a second capsules pressingmechanism.

Mounting assembly 1506 may be substantially the same as mountingassembly 116 disclosed in reference to FIG. 1. In one embodiment,mounting assembly 1506 may be a carousel that is rotatable about acentral axis so as to align fluid dispensing assembly 1502 and/orcapsule pressing mechanism 1504 with a reagent cartridge or reagentcapsule positioned below mounting assembly 1506. Mounting assembly 1506may also be linearly translatable such that fluid dispensing assembly1502 and capsule pressing mechanism 1504 may move from one reactionstation to the next.

Fluid dispensing assembly 1502 may be any fluid dispensing assembly 1502suitable for dispensing a fluid onto an underlying reagent cartridge.Representatively, in one embodiment, fluid dispensing assembly 1502 mayinclude fluid dispensing cartridge 1508 connected to cartridge pumpassembly 1510. Fluid dispensing cartridge 1508 may include a containerfor holding a fluid (e.g. a reagent) connected to a tube member fordispensing the fluid onto an underlying reagent cartridge. Cartridgepump assembly 1510 may be a pump mechanism dimensioned to pump the fluidfrom fluid dispensing cartridge 1508.

Capsule pressing mechanism 1504 may also be mounted to mounting assembly1506. Capsule pressing mechanism 1504 may be substantially the same ascapsule pressing mechanism 1000 described in reference to FIGS. 10A-10D.In this aspect, capsule pressing mechanism 1504 may include housing 1516and piston 1512. Spring member 1514 may further be positioned aroundpiston 1512 to bias piston 1512 in a raised position. An actuator (notshown) as previously discussed in reference to FIGS. 10A-10D may bepositioned concentrically inward from capsule pressing mechanism 1504 todrive movement of piston 1512.

During operation, mounting assembly 1506 moves from one reaction stationto the next and may further rotate to align fluid dispensing assembly1502 and capsule pressing mechanism 1504 with the desired station. Insome embodiments, mounting assembly 1506 having fluid dispensingcartridges therein may complete a cycle (e.g. complete a pass by eachreaction station) every 3 minutes. In this aspect, where there are 30reaction stations, mounting assembly 1506 passes by each reactionstation every 6 seconds, with approximately 2-3 seconds at each reactionstation for dispensing of the reagent.

FIGS. 16A and 16B illustrate perspective views of one embodiment of anoverhead fluid dispensing system. Referring to FIG. 16A, fluiddispensing system 1600 generally includes fluid dispensing assembly 1602and bulk reagent dispenser 1604. Fluid dispensing assembly 1602 issubstantially similar to fluid dispensing assembly 1502 described inreference to FIG. 15. In this aspect, fluid dispensing assembly 1602includes a mounting assembly that is rotatable and linearly translatableacross the underlying reaction stations 1606. Mounting stations 1618 areprovided on the mounting assembly for mounting of reagent dispensingcartridges and/or capsule pressing mechanisms.

Fluid dispensing system 1600 further includes bulk fluid dispensingassembly 1604. Bulk fluid dispensing assembly 1604 is used to dispensebulk fluids into bulk fluid reservoirs 1614 of reaction stations 1606 asdiscussed in reference to FIG. 11. In this aspect, bulk fluid dispensingassembly 1604 includes nozzle bracket 1608 for supporting nozzles 1610.Nozzles 1610 are connected to supply lines 1612. Each of supply lines1612 are connected to a respective bulk container. As previouslydiscussed in reference to FIG. 11, a single supply line 1612 from adesired bulk container may be used to fill bulk fluid reservoirs 1614.In this aspect, each of supply lines 1612 may be fluidly connected to adifferent bulk container. The number of nozzles 1610 and associatedsupply lines 1612 may vary depending upon the number of different bulkfluids desired. Representatively, in one embodiment, six nozzles 1610and six supply lines 1612 extending from six different bulk containersmay be connected to nozzle bracket 1608.

Nozzle bracket 1608 may be linearly translatable across the underlyingreaction stations 1606. In this aspect, nozzle bracket 1608 may bemovably connected by support arms 1620 to bracket rail 1616. Bracketrail 1616 may extend along a back end of reaction stations 1606. Nozzlebracket 1608 extends from bracket rail 1616 over reaction stations 1606.Nozzle bracket 1608 and the associated supply lines 1612 and nozzles1610 may be moved along bracket rail 1616 by another x axis andpositioned over the desired bulk fluid reservoir 1614. Once nozzlebracket 1608 is positioned over the desired bulk fluid reservoir 1614,one of nozzles 1610 associated with the desired bulk fluid may beactuated to dispense the desired bulk fluid into bulk fluid reservoir1614. Bulk fluid dispensing assembly 1604 moves independently from fluiddispensing assembly 1602. In this aspect, during operation, bulk fluiddispensing assembly 1604 may be one or more stations ahead of fluiddispensing assembly 1602.

Fluid dispensing system 1600 may further include reagent cartridgescanner 1622 attached to nozzle bracket 1608. Reagent cartridge scanner1622 may be any type of scanner suitable for reading identifiers such asradio frequency identification (RFID) tags, shape identifiers, coloridentifiers, numbers or words, other optical codes, barcodes etc.associated with reagent cartridges positioned on reaction stations 1606(e.g. identifier 920 illustrated in FIG. 9A). In this aspect, reagentcartridge scanner 1622 includes a reading window at end 1624. Whenreagent cartridge 1634 is positioned on one of mounting bases 1632, anidentifier positioned along an end of reagent cartridge 1634 is alignedwith the reading window at end 1624. The identifier may be read byreagent cartridge scanner 1622 through the reading window. Reagentcartridge scanner 1622 moves horizontally along bracket rail 1616 fromone reaction station 1606 to the next reading an identifier associatedwith a reagent cartridge mounted at each reaction station 1606. Althoughreagent cartridge scanner 1622 is shown mounted to nozzle bracket 1608,it is further contemplated that reagent cartridge scanner 1622 andnozzle bracket 1608 may be mounted to different bracket assemblies suchthat they are independently movable.

In addition to reagent cartridge scanner 1622, fluid dispensing system1600 may include slide scanner 1628. Although only one slide scanner1628 is illustrated in FIG. 16A, it is to be understood that fluiddispensing system 1600 includes a second slide scanner as illustrated inFIG. 18 that is substantially the same as slide scanner 1628. Slidescanner 1628 may be any type of scanner suitable for reading identifierssuch as radio frequency identification (RFID) tags, shape identifiers,color identifiers, numbers or words, other optical codes, barcodes etc.associated with slide 1638 positioned on reaction station 1606. Slidescanner 1628 may be attached to fluid dispensing assembly 1602positioned above reaction station 1606 by scanner bracket 1630. Scannerbracket 1630 may be attached to a non-rotatable support member of fluiddispensing assembly 1602 such that it moves linearly along with fluiddispensing assembly 1602 but does not rotate. In this aspect, slidescanner 1628 can be moved from one reaction station 1606 to the nextalong with fluid dispensing assembly 1602. Alternatively, slide scanner1628 may be linearly and rotatably translatable along with fluiddispensing assembly 1602. In still further embodiments, scanner bracket1630 of slide scanner 1628 may be directly attached to rail 1616 suchthat it may be moved independently from fluid dispensing assembly 1602.

Mirror 1626 may be positioned within each reaction station 1606 tofacilitate reading of identifier 1640 associated with slide 1638 (seeFIG. 16B) positioned within reaction station 1606. As illustrated inFIG. 16B, identifier 1640 is located at an end of slide 1638, preferablyon a frosted region of slide 1638. Slide 1638 is positioned withinreaction chamber 1646 of reaction station 1606 so that the samplemounted on slide 1638 and identifier 1640 are face down. Mirror 1626 ispositioned below the end of slide 1638 including identifier 1640 suchthat image 1642 of identifier 1640 is reflected in mirror 1626. Mirror1626 is positioned so that image 1642 is reflected in a direction ofslide scanner 1628 as illustrated by arrow 1644. Slide scanner 1628reads identifier 1640 by scanning image 1642 of identifier 1640 frommirror 1626. In some embodiments, mirror 1626 may be a disposable mirrorthat can be removed and replaced with a new mirror by a user. As such,if mirror 1626 becomes scratched or otherwise unsuitable for use, theuser can immediately replace it without the need to call for service.Alternatively, mirror 1626 may be fixedly mounted within reactionstation 1606. As will be discussed in more detail in reference to FIGS.22-24, information obtained by reagent cartridge scanner 1622 from theidentifier on the reagent cartridge and by slide scanner 1628 fromidentifier 1640 on slide 1638 may be used to verify a processingprotocol performed on the sample mounted on slide 1638.

FIG. 17 illustrates a top view of an embodiment of bulk fluid dispensingassembly. Bulk fluid dispensing assembly 1604 is substantially the sameas the bulk fluid dispensing assembly described in reference to FIG.16A. From this view, the positioning of nozzles 1610 over bulk fluidreservoir 1614 of reaction station 1606 can be seen. It is noted thatreagent cartridge scanner 1622 and reagent cartridge mounting member1632 are omitted so that the relationship between nozzles 1610 and bulkfluid reservoir 1614 can be more clearly seen. Once positioned asillustrated, a desired fluid from the bulk reagent container may bepumped through supply line 1612 and out nozzle 1610 to the desiredreservoir 1614. Once the desired amount of fluid is pumped intoreservoir 1614, bulk fluid dispensing assembly 1604 may be moved in adirection of arrow 1620 to the next reaction station for dispensing of asame or different reagent into the reservoir.

FIG. 18 illustrates a top view of an embodiment of a fluid dispensingsystem. The geometry and mechanism of fluid dispensing system 1800 isvariable depending on the operation of the fluid dispensing assemblyselected for use with system 1800. System 1800 includes mountingassembly 1802 having a plurality of mounting stations 1804 at whichfluid dispensing cartridge 1806 may be mounted. Mounting assembly 1802may be substantially the same as mounting assembly 1506 described inreference to FIG. 15. Fluid dispensing cartridge 1806 may besubstantially the same as fluid dispensing cartridge 1502 described inreference to, for example, FIG. 15.

Mounting stations 1804 preferably include mounting apertures 1808 forselectively positioning a plurality of fluid dispensing cartridges 1806.In one embodiment, one or more of mounting stations 1804 may includemounting aperture 1834 dimensioned for positioning of capsule pressingmechanism 1836. A cartridge pump assembly such as cartridge pumpassembly 1510 previously discussed in reference to FIG. 15 is mounted toeach of stations 1804 holding fluid dispensing cartridges 1806.Actuators 1814 and 1816 of actuator assembly 1820 may be aligned withthe pump assembly of cartridges 1806 to activate the pump assembly whendesired. In addition, one of actuators 1814 or 1816 may be aligned withcapsule pressing mechanism 1836. Since there are two actuators 1814 and1816, reagent from two different fluid dispensing cartridges 1806 can bedispensed at the same time at different locations. Alternatively, one ofactuators 1814 and 1816 may be aligned with a fluid dispensing cartridge1806 while the other is aligned with capsule pressing mechanism 1836 tofacilitate delivery of the reagent from both cartridge 1806 and acapsule mounted on one of reaction stations 1812. In still furtherembodiments, two capsule pressing mechanisms 1836 may be mounted tomounting assembly 1802 and actuators 1814 and 1816 aligned with eachcapsule pressing mechanism 1836.

System 1800 further includes bulk fluid dispensing assembly 1824. Bulkfluid dispensing assembly 1824 may be substantially the same as bulkfluid dispensing assembly 1604 described in reference to FIG. 16A. Inthis aspect, bulk fluid dispensing assembly 1824 includes nozzle bracket1826 having nozzles 1830 and reagent cartridge scanner 1832 positionedthereon. Nozzle bracket 1826 slides along bracket rail 1828 aspreviously discussed in reference to FIG. 16A.

Fluid dispensing system 1800 also includes receiving assembly 1810having a plurality of reaction stations 1812. Reaction stations 1812 maybe similar to the reaction stations previously discussed. Generallyspeaking, receiving assembly 1810 is positioned beneath mountingassembly 1802 and bulk fluid dispenser 1824 taking advantage of gravityto deliver fluids dispensed from fluid dispensing cartridges 1806 andbulk fluid dispenser 1824. Preferably, mounting assembly 1802, bulkfluid dispenser 1824 and receiving assembly 1810 are movable withrespect to one another so that the plurality of cartridges 1806 and bulkfluid dispenser 1824 can be positioned to dispense fluids onto any ofthe desired reaction stations 1812. Any combination of movability ofmounting assembly 1802, bulk fluid dispenser 1824 and reaction stations1812 may be selected. For example, each of mounting assembly 1802 andbulk fluid dispenser 1824 may be movable while reaction stations 1812are stationary. Alternatively, reaction stations 1812 may be movable andmounting assembly 1802 and bulk fluid dispenser 1824 stationary. Inaddition, as previously discussed, mounting assembly 1802 may be acarousel that is rotatable about a central axis so as to aligncartridges 1806 with the desired reaction station 1812. Mountingassembly 1802 may also be linearly translatable such that it may movefrom one reaction station 1812 to the next. Bulk fluid dispenser 1824may further be linearly translatable such that it may move from onereaction station 1812 to the next ahead or behind mounting assembly1802. Reaction stations 1812 may all be the same type of items, such asslides or alternatively may include different types of items such asslides and containers.

In one example of operation of dispensing system 1800, mounting assembly1802 is rotated so that individual cartridges 1806 or capsule pressingmechanism 1836 are selectively positioned adjacent one or both ofactuator assembly 1820. In some embodiments, system 1800 may include aplurality of actuator assemblies 1820 which are positioned adjacent toeach cartridge 1806 and capsule pressing mechanism 1836 such thatrotation of mounting assembly 1802 to align each cartridge 1806 andcapsule pressing mechanism 1836 with actuator assembly 1820 is notrequired.

Actuator assembly 1820 can be any activation device that triggerscartridge 1806 to emit a controlled amount of fluid. Representatively,actuator assembly 1820 may include a piston mechanism that aligns with,for example, an actuator of the cartridge pump assembly or capsulepressing mechanism.

Mounting assembly 1802 may be both translated and rotated with respectto receiving assembly 1810 so that an individual cartridge 1806 can beselectively positioned above any reaction station 1812. Once cartridge1806 is positioned above one of receiving members 1812, actuatorassembly 1820 triggers cartridge 1806 to emit a controlled amount offluid onto reaction station 1812.

As seen in FIG. 18, in one embodiment, mounting assembly 1802 isrotatably attached to support member 1822 while actuator assembly 1820is fixedly attached to support member 1822 such that cartridges 1806 andcapsule pressing mechanism 1836 can be rotated with respect to actuatorassembly 1820. Actuator assembly 1820 is fixedly attached to supportmember 1822, optionally beneath mounting assembly 1802. Preferably,support member 1822 can be translated horizontally such that thecartridges 1806 and capsule pressing mechanism 1836 can be both rotatedand translated with respect to the receiving members 1812. In thismanner, a chosen cartridge 1806 can be selectively positioned above anyreaction station 1812. Similarly, a chosen capsule pressing mechanism1836 can be positioned above a desired reaction station 1812.

Slide scanners 1838, 1840 may also be attached to support member 1822such that they may be moved from one reaction station 1812 to the nextalong with mounting assembly 1802. In one embodiment, slide scanners1838, 1840 may be positioned along opposite sides of mounting assembly1802. In still further embodiments, slide scanners 1838 may bepositioned within dispensing system 1800 in any matter suitable forreading identifiers on slides positioned within dispensing system 1800.

Although reaction stations 1812 are shown linearly positioned withinreceiving assembly 1810, it is further contemplated that reactionstations 1812 may be divided into two or more rows. In this aspect,actuator assembly 1820 may optionally include two or more actuators, forexample, two actuators 1814, 1816 used to dispense fluid onto two rowsof receiving members. In operation, actuator 1814 is adapted to dispensefluids onto reaction stations 1812 in one row and actuator 1816 isadapted to dispense fluids onto reaction stations 1812 in another row.It is further contemplated that any number of actuators and/or receivingmembers can be employed.

FIG. 19 illustrates a schematic diagram of a sample processing systemincluding a bulk reagent sensing assembly. During sample processing,there may be several reagents that are required in large quantities. Forexample, processing may require reagents to rinse antibodies ordetection reagents such as distilled water and buffer solutions. Suchreagents are stored in bulk containers within the system. In addition,reagent waste is disposed into bulk containers. It is often difficultfor a user to determine the amount of reagent remaining within each ofthe bulk containers or whether a bulk waste container is full. This canresult in the user failing to replace (or refill) a bulk container.System operation may in turn be delayed because the desired reagent isnot available or a waste container is too full to accept more waste.

In this aspect, sample processing system 1900 may include bulk reagentsensing assembly 1902. Bulk reagent sensing assembly 1902 may includesensors 1904, 1906, 1908 and 1910 for detecting the amount of liquid(e.g. reagent) within bulk containers 1912, 1914, 1916 and 1918,respectively. In some embodiments, sensors 1904, 1906, 1908 and 1910 maybe sensors which are capable of measuring a weight of bulk containers1912, 1914, 1916 and 1918 positioned thereon. Representatively, one ormore of sensors 1904, 1906, 1908 and 1910 may be a load cell weightsensor that converts a force applied to the sensor by the weight of thecontainer into an electrical signal such as that available from MinebeaCo., Ltd of Miyota-machi, Kitasaku-gun, Nagano, Japan.

A weight and volume of each of bulk containers 1912, 1914, 1916 and 1918may be known. In addition, the type of liquid within bulk containers1912, 1914, 1916 and 1918 and the density of the liquid may also beknown. To determine a volume of the liquid within, for example, bulkcontainer 1912, the weight of bulk container 1912 (in the absence ofliquid) may be subtracted from the weight measured by sensor 1904 (massof bulk container and liquid). The weight of the liquid within container1912 and the density of the liquid may then be used to calculate thevolume of fluid within container 1912. A determination of how full orempty the container is may then be determined by subtracting the volumeof liquid in container 1912 from the known container volume. Althoughmeasuring of a liquid within bulk container 1912 is described herein, asimilar calculation may be performed using bulk containers 1914, 1916and 1918 and sensors 1906, 1908 and 1910, respectively, to measure avolume of liquid within bulk containers 1914, 1916 and 1918. Inaddition, although four weight sensors 1904, 1906, 1908 and 1910 areillustrated in FIG. 19, it is contemplated that the number of sensorsmay vary depending upon the number of desired bulk containers in thesystem.

In still further embodiments, system 1900 may include light source 1920,1922, 1924 and 1926 to facilitate visual inspection of a liquid levelinside of containers 1912, 1914, 1916 and 1918, respectively. One ormore of light source 1920, 1922, 1924 and 1926 may be a light-emittingdiode (LED) positioned next to a respective container. Alternatively,one or more of light source 1920, 1922, 1924 and 1926 may be any lightsource capable of illuminating containers 1912, 1914, 1916 and 1918 sothat that a liquid level therein can be visualized. It is furthercontemplated that a material of containers 1912, 1914, 1916 and 1918 maybe selected to facilitate visual inspection of a liquid within thecontainer. Representatively, containers 1912, 1914, 1916 and 1918 may bemade of a semi-transparent or transparent material.

Operation of processing system 1900 and bulk reagent sensing assembly1902 will now be described. According to one embodiment, bulk container1912 may be a waste container and each of bulk containers 1914, 1916 and1918 may hold a reagent. A reagent from one or more of bulk containers1914, 1916 and 1918 may be dispensed into reservoir 1928 of a desiredreaction station by bulk reagent dispenser 1930. Pumps 1932, 1934, 1936may be associated with each supply line 1938, 1940, 1942, respectively,of bulk reagent dispenser 1930 to pump the reagent from the respectivebulk container. Once a desired reagent is within reservoir 1928, thereagent may be pumped to reaction chamber 1944 with the aid of pump1946. After processing with the reagent in reaction chamber 1944 iscompleted, the reagent may be pumped from reaction chamber 1944 to wastebulk container 1912 with the aid of pump 1948 through solenoid valve1950. In addition, once the reagent within reservoir 1928 is no longerneeded, it may be drained into bulk container 1912 with the aid of pump1948 by switching the line of solenoid valve 1950.

Sensor 1904 may continuously or periodically calculate a volume of wastewithin bulk container 1912. When the volume of liquid within bulkcontainer 1912 is above a predetermined level (e.g. the container isfull), the system alerts the user. Similarly, sensors 1906, 1908, 1910may continuously or periodically calculate a volume of liquid withinbulk containers 1914, 1916, 1918, respectively. When the volume ofliquid is below a predetermined level (e.g. the container is empty), thesystem alerts the user. Upon receiving the alert, the user may refill,replace or empty the bulk container. In addition, the system mayautomatically switch from an empty reagent container to one that has asufficient amount of the desired liquid. The system may alsoautomatically switch from a waste bulk container that is full to onethat is empty. In this aspect, where the user is not able to immediatelyattend to the bulk containers, processing may continue uninterrupted.

FIG. 20 is an illustration of one embodiment of an automated sampleprocessing system. Automated sample processing system 2000 includes acontrol computer 2002 in communication with a plurality of stainers 2004and may provide a centralized user interface for controlling theplurality of stainers 2004. Stainers 2004 may be used to processbiological specimens as previously discussed. Control computer 2002 maycommunicate with stainers 2004 in any manner known in the art, forexample control computer 2002 may communicate with stainers 2004 via ahigh-speed hub 2006. High-speed hub 2006 enables system 2000 to quicklyconvey information between the plurality of stainers 2004 and the othercomponents such as control computer 2002. For example, stainers 2004 maydownload staining protocols to be applied to slides placed in thereaction stations on stainers 2004 over a network formed by data lines2008 and high-speed hub 2006. It shall be appreciated that controlcomputer 2002 and stainers 2004 may be configured to communicate throughhardwires or wirelessly, for example, the system may utilize data lines2008, as described above, which may be conventional conductors or fiberoptics. Additionally, the components may communicate wirelessly usingradio frequency communication, such as BLUETOOTH® (a registeredtrademark of Bluetooth SIG, Inc., of Bellevue, Wash.), or any otherwireless technology.

Control computer 2002 may also communicate with one or more localdatabases 2010 so that data may be transferred to or from localdatabases 2010. For example, local database 2010 may store a pluralityof staining protocols that are designed to be performed by reactionstations on stainers 2004. The staining protocols may include a seriesof staining operations that are to be performed on slides positionedwithin the reaction stations. The staining protocols implemented byreaction stations on stainers 2004 may be chosen based on informationobtained from identifiers (e.g., barcodes, radio frequencyidentification devices (RFID), etc.) associated with the systemcomponents (e.g., on microscope slides, reagent cartridges, fluiddispensing cartridges, reagent containers, etc.). Control computer 2002may process identification data received from the reaction stations onstainers 2004 and retrieve staining protocols from local database 2010and transmit the staining protocols to the reaction stations on stainers2004. Furthermore, control computer 2002 may use local databases 2010for storage of information received from reaction stations on stainers2004, such as reports and/or status information.

Control computer 2002 may also communicate with one or more remotedatabases 2012 and/or a server 2014. Control computer 2002 maycommunicate with remote database 2012 directly or through server 2014,which may be a laboratory information system (LIS). Control computer2002 may communicate with server 2014 via a network 2016. As notedabove, server 2014 may communicate with remote database 2012. Server2014 and remote database 2012 may be used to provide staining protocolsto be used by the reaction stations on stainers 2004 in a similarfashion as local database 2010 or to supplement the protocols providedby local database 2010.

Automated processing system 2000 may optionally include one or moreprinters 2018. Printer 2018 may communicate directly with controlcomputer 2002, as shown, or directly with stainers 2004. Furthermore,stainers 2004 may each have a dedicated printer 2018 that may beintegrated into the stainer or free-standing, or multiple stainers 2004may share one or more printers.

Automated reagent dispensing system 2000 may also include a hand-held ordesktop scanner 2020 for reading identifiers that may be includedthroughout the system components (e.g., on microscope slides, reagentcartridges, fluid dispensing cartridges, reagent containers, etc.). Anytype of scanner 2020 may be utilized that is capable of interpreting theidentifiers. For example, scanner 2020 may be an RFID scanner, a 1D or2D barcode scanner, or any other type of scanner known in the art.Scanner 2020 may communicate directly with control computer 2002 orstainers 2004 and each component may have a dedicated scanner.

The system may also be powered by an uninterruptible power supply 2022.Uninterruptible power supply 2022 may be used to limit thesusceptibility of the system to general power failures that mayinvalidate tests that are interrupted. Such an interruption in powercould also result in the tissue samples becoming unusable which couldrequire gathering additional specimens. Power supply 2022 may be used topower any or all of the components of automated processing system 2000.

Although control computer 2002 is shown networked with multiple stainers2004 in FIG. 20, it shall be appreciated that the stainers 2004 may becombined in a single unit with an onboard control computer, in additionto any other component described above in the automated reagentdispensing system. Such a combination may provide a compact, stand-aloneunit that may be used to process lower volumes of biological specimens.

As previously discussed, one or more processing protocols may bedownloaded to stainers 2004. Reaction stations on stainers 2004 may thenimplement the processing protocol on slides placed in the reactionstations on stainers 2004 independent of control computer 2002. In thisaspect, if control computer 2002 stops (e.g. crashes or freezes), theprocessing protocol being run on a slide within reaction stations onstainers 2004 may continue uninterrupted.

In addition, a processing protocol performed at the reaction stations onstainers 2004 may be monitored by control computer 2002. For example,once a staining operation designated by the processing protocol iscompleted at a reaction station on one or more of stainers 2004, astaining status report may be sent to control computer 2002 notifyingcontrol computer 2002 that the staining operation has been completed. Insome embodiments, a report is sent to control computer 2002 at regularintervals (e.g. every 2-3 seconds). All staining operations completedbetween intervals may be reported to control computer 2002. In thisaspect, a staining operation that takes more than 3 seconds, for example5 seconds, will not be reported to control computer 2002 in the reportsent while the operation is still pending (i.e., the report sent 2-3seconds into the 5 second operation). Instead, performance of thestaining operation will be reported to control computer 2002 with thesubsequent report issued after the staining operation has beencompleted. Alternatively, a staining operation may be reported at anytime prior to completion. In addition, if stainer 2004 is unable to sendthe staining status report at the regular interval (e.g., controlcomputer 2002 loses power), the reports that were not sent will becompiled at stainer 2004 and sent together to control computer 2002 whenreporting is resumed (e.g., power is restored).

A staining log of each of the operations performed on strainers 2004 maybe created by control computer 2002 based on the status report anddisplayed on control computer 2002. In this aspect, control computer2002 can display all necessary staining logs to the user when desired.In some embodiments, in addition to the staining operations completed onstrainers 2004, the staining log may include, for example,identification information relating to the system components (e.g.,microscope slides, reagent cartridge, fluid dispensing cartridges, bulkreagent containers, etc.). Representatively, the staining log mayinclude information relating to the fluid dispensing cartridges or bulkreagent containers such as a listing of the reagents within the systemthat may be used during operation of strainers 2004. Informationrelating to the reagent cartridges may include, for example, theidentity of an antibody (e.g. a primary antibody) within the reagentcartridge attached to a reaction chamber. Information relating to theslides may include, for example, a patient identification number orinformation relating to an agent such as an antibody that is to beapplied to the slide.

FIG. 21 illustrates a flow chart of one embodiment of a sampleprocessing procedure. Sample processing is initiated once a startcondition is detected. Sample processing procedure 2100 may include aninitialization procedure that occurs once a start condition is detected(block 2102). A start condition may be, for example, closing the coveron the housing of a stainer included in the automated reagent dispensingsystem, receiving a start signal from a control computer, or any othercondition. If a start condition is not detected, the automated reagentdispensing system may continually check whether a start condition isdetected until a start condition is detected.

The initialization procedure occurs after a start condition is detectedand may include taking an inventory of system components, for example,the reaction stations, reaction chambers, reagent cartridges, fluiddispensing cartridges and/or bulk reagent containers (block 2104).Inventory of the fluid dispensing cartridges, reagent cartridges andbulk containers may be taken by scanning identifiers located on thereaction stations, cartridges and containers within the system.Representatively, scanning may be performed by reagent cartridge scanner1608 and/or slide scanner 1628 located on the linearly translatablemounting assembly as illustrated in FIG. 16A. In the case of slidescanner 1628, slide scanner 1628 may move with mounting assembly alongthe reaction stations and scan identifiers located on the slidesassociated therewith. This enables the system to determine whichreaction stations include specimens and may further allow the system toidentify the proper agent (e.g., primary antibody) to be applied to theslide. After scanning the identifiers, the mounting assembly returns toa home position. In addition, by scanning the reagent cartridges using,for example reagent cartridge scanner 1608, the system may identify thetype and quantity of a reagent present in each reagent cartridge. Adetermination as to the proper processing protocol to apply to the slidemay be made using this information.

In addition, assessing the fluid volume level of, for example the bulkcontainers, obtained from the sensors may be part of the inventoryprocedure. Maintaining a history of the quantity of a liquid that hasbeen dispensed from the bulk containers may further assist in making thedetermination regarding the fluid volume level within the containers.After determining the fluid volume level, a signal may be output toprovide the user with an indication regarding how much and what types offluids are stored in the containers. Where the system determines that acontainer is empty or contains an insufficient amount of fluid toperform a predetermined staining process, the system may initiate areplacement signal indicating that one or more containers have aninsufficient amount of fluid and need to be replaced or refilled. Thesystem may further automatically select a different container whichcontains a sufficient volume of the desired fluid, if available, so thatprocessing may continue uninterrupted.

Once the inventory procedure is completed, instruction sequences arereceived by the reaction stations (block 2106) and the stainingprotocols downloaded to each reaction station are run (block 2108). Astaining protocol may include a sequence of processing operationsincluding, in any order and at various times, dispensing a primaryreagent from a reagent cartridge associated with a reaction station,dispensing a secondary reagent from a fluid dispensing cartridge mountedin the overhead mounting assembly, dispensing a further reagent from abulk fluid dispensing assembly positioned above the reaction stationand/or dispensing a reagent into the reaction station through inletports within the reaction station.

FIG. 22 illustrates a flow chart of an embodiment of a sample processingprocedure. Typically, an operator, such as a lab technician, isentrusted with the responsibility of ensuring that a slide having asample mounted thereon has been placed within the correct reactionstation and processed according to a processing protocol assigned tothat station. If, however, the operator mistakenly places the slide inthe wrong station, the wrong processing protocol may be performed on thesample on the slide. Such mistake may not be discovered until the slidehas been removed from the station and analyzed by, for example, thepathologist days or in some cases weeks later. Since the slide is nolonger in the station, it may be difficult to determine the processingprotocol performed on the slide and in turn whether the slide should beprocessed again or whether processing must be performed on a new slidehaving a new sample. Such error, may therefore cause significant delaysin result analysis and reporting. Still further, where the error inprocessing is not detectable by the pathologist upon review of thesample, the mistake may go unnoticed leading to an incorrectrecommendation or diagnosis.

The sample processing procedure illustrated in FIG. 22 may be used toverify a processing protocol performed on a sample mounted on a slide.In this aspect, procedure 2200 may include placing a first identifier ona front side of a slide (i.e., side with sample mounted thereon)(block2202). The first identifier may be, for example, an identifier such asidentifier 1640 described in reference to FIG. 16B. The identifier mayinclude information such as patient information and/or the name of anagent, for example, an antibody, to be applied to the slide. The slideis then placed back side up (i.e., side opposite the sample) in areaction chamber mounted to a reaction station for processing (block2204). Once the slide is in place, a reagent cartridge is mounted to thereaction chamber (block 2206). The reagent cartridge may be a reagentcartridge such as reagent cartridge 408 described in reference to FIG.4A. The reagent cartridge may have a second identifier, such asidentifier 920 described in reference to FIG. 9A, positioned thereon.The second identifier may identify, for example, an antibody associatedwith the reagent cartridge. The antibody, may be, for example, foundwithin a capsule (see, reagent capsule 900 of FIG. 9A) attached to thereagent cartridge.

The first identifier located on the slide is scanned (block 2208) andthe second identifier located on the reagent cartridge is scanned (block2210). A processing protocol to be applied to the sample on the slide isdetermined based on information obtained from the second identifier(block 2212). Representatively, the second identifier may identify areagent within the reagent cartridge. Alternatively, the processingprotocol to be applied to the sample on the slide may be determinedbased on information from the first identifier. The control computer maythen use this information to select a processing protocol that may berun using the identified reagent. It is further contemplated that anoperator may select a protocol based on the identified reagent. Theselected processing protocol may be performed on the sample found on theslide (block 2214). Information obtained from the first identifierlocated on the slide may be associated with information obtained fromthe second identifier located on the reagent cartridge to confirm theprocessing protocol performed on the sample on the slide (block 2216).The information from the first identifier and the second identifier maybe associated during processing of the sample according to theprocessing protocol or upon completion of the processing. The associatedinformation may be displayed on the control computer so that theoperator may determine whether the correct processing protocol wasassigned to the correct slide.

FIG. 23 illustrates an embodiment of a display associated with a sampleprocessing procedure. Display 2300 illustrates the information obtainedfrom the first identifier and the information obtained from the secondidentifier. In this aspect, display 2300 includes reagent cartridgeidentification table 2302 and slide identification table 2304. Reagentcartridge identification table 2302 includes station identificationcolumn 2306 and reagent identification column 2308. Stationidentification column 2306 identifies the reaction station that thereagent cartridge is located on. Reagent identification column 2308identifies a reagent located in the reagent cartridge. Representatively,upon review of reagent identification table 2302 illustrated in FIG. 23an operator will understand that a reagent cartridge having antibody LCAis located at stations 2, 16 and 17, a reagent cartridge holdingantibody CD30 is located at stations 3 and 5, a reagent cartridgeholding antibody Desmin is located at station 9, a reagent cartridgeholding antibody Cytokeratin7 is located at station 10 and a reagentcartridge holding antibody Vimentin is located at station 12.

Similarly, slide identification table 2304 includes slide identificationcolumn 2312 and reagent identification column 2310. Upon review of slideidentification table 2304 illustrated in FIG. 23, an operator willunderstand that antibody LCA is to be applied to a slide located atstations 2, 16 and 17, antibody CD30 is to be applied to a slide locatedat stations 3 and 5, antibody Desmin is to be applied to a slide locatedat station 9, antibody Cytokeratin7 is to be applied to a slide locatedat station 10 and antibody Vimentin is to be applied to a slide locatedat station 12.

Reagent identification table 2302 and slide identification table 2304are juxtaposed so that rows having the same station number are aligned.As a result, the operator can easily review reagent identification table2302 and slide identification table 2304 and determine whether theproper antibody was applied to the proper slide. For example, slideidentification table 2304 provides that the slide located at station 2should receive antibody LCA. Reagent identification table 2306 indicatesthat the antibody located at station 2 was LCA. Based on thisinformation, the operator can confirm that a processing protocol usingLCA was properly assigned to the slide at station 2.

Reagent identification table 2302 and slide identification table 2304may be saved and associated with other run information to providetraceability information. In other words, reagent identification table2302 shows which reagent was associated with a particular station andslide identification table 2304 shows which reagent was desired to bedispensed on the slide. Saving this information (e.g., data of thegenerated tables before processing) is an indication of the processingperformed on a slide. A staining log, such as that previously disclosedin reference to FIG. 20, may include the traceability information.

Based on the information provided by display 2300, the operator canchoose to reload the stations and start another run by clicking on startrun button 2314. Alternatively, the operator can choose to re-scan theexisting samples again by clicking on the re-scan button 2316. Finally,an operator may choose to cancel the run or display by clicking oncancel button 2318.

FIG. 24 illustrates an embodiment of a display associated with a sampleprocessing procedure. Display 2400 illustrates an embodiment where thereis a mismatch of reagent information. Display 2400 is substantiallysimilar to display 2300 in that it includes reagent identification table2402 having station identification column 2406 and reagentidentification column 2408. In addition, display 2400 includes slideidentification table 2404 having slide identification column 2412 andreagent identification column 2410. Display 2400 further includesstart-run button 2414, re-scan button 2416 and cancel button 2418.

As can be seen from slide identification table 2404, the slide locatedat station 2 requires antibody CD30 and the slide located at station 3requires antibody LCA. Reagent identification table 2402, however,indicates that the antibody located at station 2 was LCA and theantibody located at station 3 was CD30. Thus, the wrong antibody, and inturn processing protocol, was assigned to the slide at station 2 and theslide at station 3. Based on this information, the operator can replacethe slide at station 2 with a slide requiring LCA and the slide atstation 3 with a slide requiring CD30 and re-scan the slides.Alternatively, the operator may replace the reagent cartridges withreagent cartridges having the proper antibody. Still further, theoperator may replace the identifier on the slide with an identifier thatproperly identifies the reagent applied to the slide sample. Othermismatch variations are further contemplated that may be displayed ondisplay 2400, for example a slide may be placed at a station with noreagent cartridge such as station 1.

It is further contemplated that in some embodiments, control computer2002 may automatically alert a user to a mismatch. Representatively,control computer 2002 may be programmed to detect mismatches betweenreagent identification table 2402 and slide identification table 2404.When a mismatch is detected, an alarm may sound to alert the user thatthe reagent identified by the identifier on the slide has not beenapplied to the slide.

A device, such as control computer 2002, for performing the operationsherein may be specially constructed for the required purposes or it maycomprise a general purpose computer selectively activated orreconfigured by a computer program stored in the computer. Such acomputer program may be stored in a computer readable storage medium,such as, but not limited to, any type of disk including floppy disks,optical disks, CD-ROMs and magnetic-optical disks, read-only memories(ROMs), random access memories (RAMs), EPROMs, EEPROMs, magnetic oroptical cards, Flash memory devices including universal serial bus (USB)storage devices (e.g., USB key devices) or any type of media suitablefor storing electronic instructions, each of which may be coupled to acomputer system bus.

FIG. 25A, FIG. 25B and FIG. 25C illustrate perspective views of anembodiment of a waste drain system within the sample processing system.Waste drain system 2500 may include waste containers 2502, 2504. Wastecontainers 2502, 2504 may be similar to bulk containers 118 described inreference to FIG. 1. Although two waste containers 2502, 2504 areillustrated, the following description may apply to any number of wastecontainers positioned within the sample processing system. In addition,although the containers are described as waste containers, it iscontemplated that the containers may be any type of bulk container usedto hold any type of fluid (e.g. a reagent or wash fluid).

Waste containers 2502, 2504 may be positioned within the sampleprocessing system below the reaction compartment holding the reactionstations as described in reference to FIG. 1. Waste containers 2502,2504 may rest upon sensing plate 2514. Sensing plate 2514 may be similarto sensor 1904 described in reference to FIG. 19. In this aspect,sensing plate 2514 may be used to detect a fluid level within wastecontainers 2502, 2504. Drain tubes 2506, 2508 may be aligned with wastecontainers 2502, 2504, respectively, to help direct a waste fluid fromthe reaction stations into waste containers 2502, 2504. Duringoperation, it may be desirable to raise or lower drain tubes 2506, 2508depending on whether filling or removal of waste containers 2502, 2504is desired. For example, during a processing operation it is desirablefor drain tubes 2506, 2508 to be lowered within waste containers 2502,2504 so that waste is deposited directly into containers 2502, 2504.Drain tubes 2506, 2508 are then raised to facilitate changing, replacingor emptying of waste containers 2502, 2504. In this aspect, levers 2510,2512 are attached to drain tubes 2506, 2508, respectively, to raise orlower drain tubes 2506, 2508. FIG. 25A illustrates an embodiment wherelever 2510 is lowered and drain tube 2506 is lowered into wastecontainer 2502 while lever 2512 is raised and drain tube 2508 is raisedabove waste container 2504.

Drain tubes 2506, 2508 are fluidly connected to connecting tubes 2516,2518, respectively, as illustrated in FIG. 25B. Connecting tubes 2516,2518 provide a fluid conduit for waste to travel from the reactionstations to drain tubes 2506, 2508. Connecting tubes 2516, 2518 may havea modifiable configuration such that they provide a sloped-down conduitwhen drain tubes 2506, 2508 are lowered within waste containers 2502,2504 and a sloped-up conduit when drain tubes 2506, 2508 are raisedabove waste containers 2502, 2504. Each of connecting tubes 2516, 2518may be independent from one another and therefore independentlymodifiable. In this aspect, connecting tube 2518 may be a jointed tubehaving first joint 2528 proximal to drain tube 2508 and second joint2530 distal to drain tube 2508. Connecting tube 2518 may be made ofsections of a rigid material such as a metal or rigid plastic materialor a more flexible material such as a flexible plastic connected byjoints 2528, 2530. Alternatively, connecting tube 2518 may be anintegrally formed tube made of a flexible plastic material that ismodifiable in the absence of joints and therefore joints 2528 and 2530may be omitted. When drain tube 2508 is raised, for example to removewaste containers 2504, the portion of connecting tube 2518 between firstjoint 2528 and drain tube 2508 is raised above the portion of connectingtube 2518 between second joint 2530 and vertical connecting member 2526while the portion of connecting tube 2518 between first joint 2528 andsecond joint 2530 has a sloped-up orientation. Connecting tube 2516 mayfurther be jointed similar to connecting tube 2518. FIGS. 25A, 25B and25C illustrate an embodiment where drain tube 2508 is raised and in turnconnecting tube 2518 includes the raised and sloped-up portionpreviously discussed, while drain tube 2506 is lowered such thatconnecting tube 2516 has a sloped-down orientation. In the case of aflexible plastic tube, similar regions of connecting tubes 2516, 2518may have raised and sloped orientations as previously discussed.

Flow of fluids through waste drain system 2500 is substantially apassive process driven primarily by gravity. As such, the ability tomodify the orientation of connecting tubes 2516, 1518 helps to control aflow of fluid through drain tubes 2506, 2508 as well as fluid back upinto the associated reaction stations. In particular, when drain tube2506 is lowered and, in turn, connecting tube 2516 has a sloped-downconfiguration, gravity drives flow of a waste fluid from waste drain2520 of the reaction station, through vertical connecting member 2524,and into connecting member 2516. Since connecting member 2516 issloped-down, fluid drained from the reaction station easily flows intodrain tube 2506 and is deposited within waste container 2502. Whenconnecting member 2518 is in a sloped-up configuration (i.e. when draintube 2508 is raised) fluid may stop flowing, and in some cases, begin toflow away from drain tube 2508 back toward waste drain 2522 of theassociated reaction station. Stopping or reversing the flow of fluid maybe desirable when, for example, waste container 2504 is being removed orreplaced by another container as it prevents waste from dripping ontosensing plate 2514 and/or the operator. It is recognized, however, thatwhen a level of fluid within connecting member 2518 reaches a levelwithin vertical connecting member 2526 above the highest point ofconnecting member 2518 (e.g. joint 2528), fluid begins to flow in adirection of drain pipe 2508 so that the fluid does not flow back intothe associated reaction station. Such feature is desirable, for example,where an operator forgets to lower drain tube 2508 into drain container2504 before starting the processing operation. Once a sufficient levelof fluid begins to collect within vertical connecting member 2526 (i.e.a fluid level above the highest point of connecting member 2518) thefluid will begin to flow through connecting member 2518 and into wastecontainer 2504 via drain tube 2508, thereby preventing waste back upwithin the reaction station.

The algorithms and displays presented herein are not inherently relatedto any particular computer or other apparatus. Various general purposesystems may be used with programs in accordance with the teachingsherein or it may prove convenient to construct a more specialized deviceto perform the described method. In addition, the invention is notdescribed with reference to any particular programming language. It willbe appreciated that a variety of programming languages may be used toimplement the teachings of the invention as described herein.

A computer readable medium includes any mechanism for storinginformation in a form readable by a computer. For example, a computerreadable medium includes read only memory (“ROM”), random access memory(“RAM”), magnetic disk storage media, optical storage media, flashmemory devices or other type of machine-accessible storage media.

It should also be appreciated that reference throughout thisspecification to “one embodiment”, “an embodiment”, or “one or moreembodiments”, for example, means that a particular feature may beincluded in the practice of the invention. Similarly, it should beappreciated that in the description various features are sometimesgrouped together in a single embodiment, Figure, or description thereoffor the purpose of streamlining the disclosure and aiding in theunderstanding of various inventive aspects. This method of disclosure,however, is not to be interpreted as reflecting an intention that theinvention requires more features than are expressly recited in eachclaim. Rather, as the following claims reflect, inventive aspects maylie in less than all features of a single disclosed embodiment. Thus,the claims following the Detailed Description are hereby expresslyincorporated into this Detailed Description, with each claim standing onits own as a separate embodiment of the invention.

In the foregoing specification, the invention has been described withreference to specific embodiments thereof. It will, however, be evidentthat various modifications and changes can be made thereto withoutdeparting from the broader spirit and scope of the invention as setforth in the appended claims. For example, a reagent cartridge asdisclosed herein (e.g. reagent cartridge 408) may contain solvent orwater instead of a reagent and used for purposes other than, forexample, staining a sample on an underlying slide. The specification anddrawings are, accordingly, to be regarded in an illustrative rather thana restrictive sense.

We claim:
 1. An apparatus comprising: a reagent cartridge having areagent retaining recess and a reagent directing channel, both thereagent retaining recess and reagent directing channel in fluidcommunication with an outlet channel extending from a bottom of thereagent cartridge; and a reaction chamber having a platen dimensioned toreceive a slide, the platen defining a reagent drip surface forreceiving a reagent dispensed from the reagent cartridge.
 2. Theapparatus of claim 1 wherein the reagent retaining recess is dimensionedto receive a reagent capsule having a reagent contained therein.
 3. Theapparatus of claim 2 wherein the reagent capsule comprises a collapsiblecontainer and a plunger dimensioned to break a seal of the containerwhen the container is collapsed.
 4. The apparatus of claim 1 furthercomprising: a first identifier and a second identifier coupled to thereagent cartridge, the first identifier and the second identifiercomprising information identifying a reagent contained within thereagent cartridge and wherein one of the first identifier and the secondidentifier is removable.
 5. The apparatus of claim 1 wherein the platenis comprised of a hydrophilic material.
 6. The apparatus of claim 1wherein the platen is comprised of a metal material having at least oneof an antimicrobial or a corrosion resistance property.
 7. The apparatusof claim 1 wherein the platen is positioned at a horizontal angle withrespect to level ground of from 5 degrees to 15 degrees.
 8. Theapparatus of claim 1 wherein the platen is positioned at a verticalangle with respect to level ground of 15 degrees to 45 degrees.
 9. Theapparatus of claim 1 further comprising at least one spacer memberextending from a surface of the platen to create an uneven gap betweenthe platen and a slide positioned on the platen.
 10. The apparatus ofclaim 1 further comprising a bulk reagent reservoir coupled to thereaction chamber the bulk reagent reservoir in fluid communication withthe reaction chamber.
 11. The apparatus of claim 1 wherein the reactionchamber further comprises: a first fluid outlet port, a second fluidoutlet port and a fluid inlet port extending through the platen, whereinthe fluid inlet port is positioned between the first fluid outlet portand the second fluid outlet port.
 12. The apparatus of claim 1 furthercomprising a temperature modifying assembly coupled to the platen tomodify a temperature of the reaction chamber.
 13. The apparatus of claim12 wherein the temperature modifying assembly comprises a thermoelectriccooler (TEC).
 14. The apparatus of claim 12 wherein the temperaturemodifying assembly comprises a heat sink and a fan to control atemperature of the temperature modifying assembly.
 15. The apparatus ofclaim 12 wherein the temperature modifying assembly comprises athermistor for monitoring a temperature of the reaction chamber.
 16. Anapparatus comprising: a reagent cartridge comprising a reagent retainingrecess; and a reagent capsule removably positioned within the reagentretaining recess.
 17. The apparatus of claim 16 wherein the reagentcartridge further comprises a reagent directing channel, the reagentretaining recess and the reagent directing channel in fluidcommunication with an outlet channel for directing a reagent out of thereagent cartridge.
 18. The apparatus of claim 16 wherein the reagentcapsule comprises a collapsible container and a plunger dimensioned tobreak a seal of the container when the container is collapsed.
 19. Theapparatus of claim 16 further comprising a bracket assembly coupled tothe capsule, the bracket assembly dimensioned to secure the capsule tothe reagent cartridge.
 20. The apparatus of claim 19 wherein the bracketassembly comprises a identifier identifying a reagent contained withinthe capsule.
 21. The apparatus of claim 19 wherein the capsule isremovably coupled to the bracket assembly.
 22. An apparatus comprising:a platen dimensioned to receive a slide; at least one spacer memberextending from a surface of the platen to create an uneven gap betweenthe platen and a slide positioned thereon; and at least one outlet portand at least one inlet port extending through the platen.
 23. Theapparatus of claim 22 wherein the platen defines a fluid drip surface atone end for receiving a fluid dispensed onto the platen from above. 24.The apparatus of claim 22 wherein the at least one spacer member is aspacer bar extending across a width dimension of the platen, the spacerbar comprising a width dimension sufficient to prevent fluid fromtraveling across the spacer bar.
 25. The apparatus of claim 22 whereinthe at least one spacer member is a first spacer member positioned atone end of the platen, a second spacer member is positioned a distancefrom the first spacer member at the one end of the platen and a thirdspacer member is positioned at an opposite end of the platen, the firstspacer member and the second spacer member having a height differentfrom the third spacer member so as to create the uneven gap between theplaten and a slide positioned thereon.
 26. The apparatus of claim 22further comprising a wall positioned around a portion of the platen, thewall comprising a height sufficient to retain a fluid dispensed onto theplaten.
 27. The apparatus of claim 22 wherein the platen comprises ahydrophilic surface.
 28. The apparatus of claim 22 wherein the platen iscomprised of a metal or a plastic material.
 29. The apparatus of claim22 wherein the at least one outlet port is a first outlet portpositioned at one end of the platen and a second outlet port ispositioned at an opposite end of the platen, the at least one inlet portis positioned between the first outlet port and the second outlet port.30. A system comprising: a linearly translatable mounting assemblyhaving a plurality of mounting stations dimensioned to receive at leastone fluid dispensing cartridge; a linearly translatable bulk reagentdispensing assembly having a plurality of bulk reagent dispensingnozzles coupled thereto; and a receiving assembly positioned beneath themounting assembly and the bulk reagent dispensing assembly, thereceiving assembly including a plurality of reaction stations.
 31. Thesystem of claim 30 wherein at least one of the plurality of mountingstations is dimensioned to receive a reagent capsule pressing mechanism.32. The system of claim 30 wherein the translatable mounting assembly isalso rotatable about an axis of rotation that is linearly translatable.33. The system of claim 30 wherein each of the plurality of bulk reagentdispensing nozzles is fluidly coupled to a bulk reagent container. 34.The system of claim 30 further comprising a reagent cartridge and areaction chamber positioned at each of the plurality of reactionstations, the reagent cartridge dimensioned to receive and direct afluid dispensed from the fluid dispensing cartridge onto the reactionchamber.
 35. The system of claim 34 wherein the reaction chambercomprises a platen having a microscope slide mounted thereon.
 36. Thesystem of claim 30 further comprising a plurality of temperaturemodifying assemblies situated at a respective one of the plurality ofreaction stations.
 37. The system of claim 36 wherein the temperaturemodifying assemblies are selectively controlled to heat and cool theplurality of reaction stations.
 38. The system of claim 36 wherein theplurality of temperature modifying assemblies are thermoelectric coolers(TEC).
 39. The system of claim 30 further comprising a bulk containerand a sensor coupled to the bulk container to determine a fluid level ofthe bulk container.
 40. The system of claim 30 wherein the sensor is aweight sensor.
 41. The system of claim 30 further comprising a lockingassembly coupled to each of the reaction stations to lock the reactionstations in position.
 42. The system of claim 41 wherein the lockingassembly is an electromechanical locking system that remains locked inthe event of a power failure.
 43. The system of claim 30 furthercomprising a waste drain assembly fluidly coupled to the plurality ofreaction stations, the waste drain assembly having a modifiable fluidconduit dimensioned to prevent waste back up into the plurality ofreaction stations.
 44. A method comprising: determining an inventory ofan automated sample processing system, the determining an inventorycomprising retrieving information from an identifier associated with atleast one reaction station in the automated sample processing system andat least one sensor associated with at least one bulk container in theautomated sample processing system; downloading a processing protocolfrom a central controller to the automated sample processing system;operating the automated sample processing system based on the processingprotocol and independently of the central controller; and dispensing areagent from the automated sample processing system.
 45. The method ofclaim 44 wherein determining an inventory comprises scanning anidentifier included on a reagent cartridge associated with the at leastone reaction station.
 46. The method of claim 44 wherein determining aninventory further comprises scanning an identifier included on a fluiddispensing cartridge used in the automated sample processing system. 47.The method of claim 44 wherein information retrieved from the sensorcomprises information relating to a volume of liquid within the bulkcontainer.
 48. The method of claim 44 wherein operating the automatedsample processing system comprises switching from a first bulk containerto a second bulk container when it is determined from the sensor thatthe first bulk container is empty.
 49. The method of claim 44 whereindispensing a reagent comprises dispensing reagents from a linearlytranslatable bulk fluid dispensing assembly fluidly coupled to the atleast one bulk container.
 50. The method of claim 44 wherein dispensinga reagent comprises dispensing the reagent from a reagent capsule anddispensing a reagent from the reagent capsule comprises: dispensing aninitial amount of reagent contained within the capsule by advancing aplunger coupled to the capsule through a seal formed on the capsule; anddispensing a remaining amount of reagent contained within the capsule bycollapsing the capsule.
 51. The method of claim 44 wherein downloadingcomprises downloading the processing protocol to the at least onereaction station.
 52. The method of claim 51 wherein the at least onereaction station implements the processing protocol independent of thecentral controller.
 53. The method of claim 44 further comprising:monitoring a status of the processing protocol performed at the at leastone reaction station; and creating a log of each of the processesperformed according to the processing protocol at the reaction station.54. A method comprising: reflecting an image of an identifier located ona slide toward a scanner; and scanning the identifier with the scanner.55. The method of claim 54 wherein the identifier comprises a firstidentifier, further comprising: scanning a second identifier located ona reagent cartridge associated with the slide; scanning a thirdidentifier located on a reaction station associated with the slide andthe reagent cartridge; and comparing information obtained from the firstidentifier, the second identifier and the third identifier to determinea processing protocol performed on the slide.
 56. The method of claim 54wherein reflecting comprises reflecting the image on a mirror.
 57. Themethod of claim 56 wherein the mirror is removably mounted to a reactionstation supporting the slide.